Is MYO7A p.Arg802Cys (c.2404C>T) pathogenic?

MYO7A p.Arg802Cys (c.2404C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.5213); Ultra-rare (popmax 0.0169%, mid); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Arg802Cys (c.2404C>T)?

MYO7A p.Arg802Cys (c.2404C>T) is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg802Cys (c.2404C>T) in the general population?

MYO7A p.Arg802Cys (c.2404C>T) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about MYO7A p.Arg802Cys (c.2404C>T)?

AlphaMissense predicts ambiguous (score 0.5213) — an in-silico prediction, not a clinical call.

MYO7A p.Arg802Cys

c.2404C>T · rs376169396 · VCV864445

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.5213 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.5213	ambiguous
REVEL	0.762	pathogenic-leaning
SaProt	LLR -7.10	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.4	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 0.0169% Middle Eastern · 1/5,908 alleles

Filtering AF 0.00205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00264% 41/1,550,954 alleles · ultra-rare exomes 30/1,398,744 · genomes 11/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,908
African / African-American	0.0041%	24,413
Admixed American	0.00384%	26,015
European (non-Finnish)	0.00287%	34,840
Finnishnot grpmax-eligible	0.00183%	54,694
Remaining individualsnot grpmax-eligible	0.00166%	60,170

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.Arg802Cys
Coding: c.2404C>T
MANE Select: NM_000260
dbSNP: rs376169396
Type: single nucleotide variant
Location: chr11:77179771 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 802: the iq 3 domain

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

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Arg802Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Arg802His Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg802= Likely benign ★ 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

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-arg802cys (accessed [today's date]).

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