Is MYO7A p.Arg823Cys (c.2467C>T) pathogenic?

MYO7A p.Arg823Cys (c.2467C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-10-03). AlphaMissense: likely benign (0.135); Very rare (popmax 0.00587%, amr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg823Cys (c.2467C>T)?

MYO7A p.Arg823Cys (c.2467C>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.Arg823Cys (c.2467C>T) in the general population?

MYO7A p.Arg823Cys (c.2467C>T) is very rare (popmax 0.00587%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg823Cys (c.2467C>T)?

AlphaMissense predicts likely benign (score 0.135) — an in-silico prediction, not a clinical call.

MYO7A p.Arg823Cys

c.2467C>T · rs995330889 · VCV930007

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00587%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.135	likely benign
REVEL	0.493	indeterminate
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00587% Admixed American · 3/51,102 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000832%

Overall 0.00104% 16/1,543,568 alleles · very rare exomes 13/1,391,304 · genomes 3/152,264 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00587%	17,034
African / African-American	0.00411%	24,359
South Asian	0.00119%	84,040
European (non-Finnish)	0.000785%	127,455

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.Arg823Cys
Coding: c.2467C>T
MANE Select: NM_000260
dbSNP: rs995330889
Type: single nucleotide variant
Location: chr11:77179834 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 823: the iq 4 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 Usher syndrome type 1B

Similar variants

MYO7A p.Arg823Pro Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg823His Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg823Gly 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

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-arg823cys (accessed [today's date]).

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