Is MYO7A p.Arg1743Trp (c.5227C>T) pathogenic?

MYO7A p.Arg1743Trp (c.5227C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-04-16). AlphaMissense: likely benign (0.3111); Rare (popmax 0.31%, nfe); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg1743Trp (c.5227C>T)?

MYO7A p.Arg1743Trp (c.5227C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg1743Trp (c.5227C>T) in the general population?

MYO7A p.Arg1743Trp (c.5227C>T) is rare (popmax 0.31%, nfe) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Arg1743Trp (c.5227C>T)?

AlphaMissense predicts likely benign (score 0.3111) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1743Trp

c.5227C>T · rs111033287 · VCV43278

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.3111 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.31%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.3111	likely benign
REVEL	0.412	indeterminate
SaProt	LLR -3.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP 1.8, phastCons 0.92
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% European (non-Finnish) · 3,561/1,147,358 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.298%

Overall 0.257% 3,978/1,549,698 alleles · rare exomes 3,651/1,397,344 · genomes 327/152,354 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.339%	295
European (non-Finnish)grpmax	0.31%	322
Finnishnot grpmax-eligible	0.297%	336
Remaining individualsnot grpmax-eligible	0.138%	722
Admixed American	0.0568%	1,762
African / African-American	0.0383%	2,612
Middle Eastern	0.0228%	4,388
East Asian	0.00488%	20,488
South Asian	0.00119%	84,006

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYO7A
Protein: p.Arg1743Trp
Coding: c.5227C>T
MANE Select: NM_000260
dbSNP: rs111033287
Type: single nucleotide variant
Location: chr11:77203118 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1743: a UniProt-annotated variant site (in ush1b)

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Arg1743= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Arg1743Gln Uncertain significance ★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/myo7a-p-arg1743trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown