Is MYO7A p.Arg804Trp (c.2410C>T) pathogenic?

MYO7A p.Arg804Trp (c.2410C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.4391); Very rare (popmax 0.00768%, amr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg804Trp (c.2410C>T)?

MYO7A p.Arg804Trp (c.2410C>T) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg804Trp (c.2410C>T) in the general population?

MYO7A p.Arg804Trp (c.2410C>T) is very rare (popmax 0.00768%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg804Trp (c.2410C>T)?

AlphaMissense predicts ambiguous (score 0.4391) — an in-silico prediction, not a clinical call.

MYO7A p.Arg804Trp

c.2410C>T · rs778880077 · VCV881167

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, amr)

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.4391	ambiguous
REVEL	0.528	indeterminate
SaProt	LLR -6.91	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	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 0.00768% Admixed American · 4/52,074 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00151%

Overall 0.000902% 14/1,551,306 alleles · very rare exomes 13/1,399,092 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00768%	13,018
Finnishnot grpmax-eligible	0.00366%	27,347
South Asian	0.00356%	28,120
Remaining individualsnot grpmax-eligible	0.00166%	60,200
African / African-American	0.00136%	73,262
European (non-Finnish)	0.000261%	383,324

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.Arg804Trp
Coding: c.2410C>T
MANE Select: NM_000260
dbSNP: rs778880077
Type: single nucleotide variant
Location: chr11:77179777 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 804: the iq 3 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Arg804Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg804= 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
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-arg804trp (accessed [today's date]).

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