Is MYO7A p.Arg1873Trp (c.5617C>T) pathogenic?

MYO7A p.Arg1873Trp (c.5617C>T) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2025-12-22). AlphaMissense: likely pathogenic (0.9923); Ultra-rare (popmax 0.0164%, mid); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Arg1873Trp (c.5617C>T)?

MYO7A p.Arg1873Trp (c.5617C>T) is associated with MYO7A-related disorder, retinal disorder, Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Arg1873Trp (c.5617C>T) in the general population?

MYO7A p.Arg1873Trp (c.5617C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about MYO7A p.Arg1873Trp (c.5617C>T)?

AlphaMissense predicts likely pathogenic (score 0.9923) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1873Trp

c.5617C>T · rs397516321 · VCV43291

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.9923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9923	likely pathogenic ✓ concordant with ClinVar
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -13.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -2.5, phastCons 0.97
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.9	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000992% 16/1,613,400 alleles · ultra-rare exomes 14/1,461,208 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00446%	22,445
Remaining individualsnot grpmax-eligible	0.0016%	62,454
Finnishnot grpmax-eligible	0.00157%	63,828
South Asian	0.0011%	90,990
European (non-Finnish)	0.000848%	117,981

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.Arg1873Trp
Coding: c.5617C>T
MANE Select: NM_000260
dbSNP: rs397516321
Type: single nucleotide variant
Location: chr11:77205598 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1873: the myth4 2 domain; an α-helix; a UniProt-annotated variant site (in ush1b)

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

Disease context

MYO7A-related disorder

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

Similar variants

MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same residue
MYO7A p.Arg1873Leu Likely pathogenic ★ same residue
MYO7A p.Arg1873= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln 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-arg1873trp (accessed [today's date]).

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