Is MYO7A p.Arg1743= (c.5227C>A) pathogenic?

MYO7A p.Arg1743= (c.5227C>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-20). Rare (popmax 0.336%, afr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg1743= (c.5227C>A)?

MYO7A p.Arg1743= (c.5227C>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg1743= (c.5227C>A) in the general population?

MYO7A p.Arg1743= (c.5227C>A) is rare (popmax 0.336%, afr) (gnomAD).

MYO7A p.Arg1743=

c.5227C>A · rs111033287 · VCV286095

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.336%, afr)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
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
Overall
CADD	9.404	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.336% African / African-American · 246/73,142 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.288%

Overall 0.0197% 305/1,549,698 alleles · rare exomes 180/1,397,344 · genomes 125/152,354 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.336%	297
Remaining individualsnot grpmax-eligible	0.0717%	1,395
Admixed American	0.0254%	3,930
European (non-Finnish)	0.000261%	382,453

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.Arg1743=
Coding: c.5227C>A
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 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg1743Gln Uncertain significance ★ ⚠ same residue
MYO7A p.Arg1743Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg1743 (accessed [today's date]).

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