Is MYO7A p.Arg88Cys (c.262C>T) pathogenic?

MYO7A p.Arg88Cys (c.262C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-03-20). AlphaMissense: likely pathogenic (0.9159); Very rare (popmax 0.00118%, sas); Associated with Monogenic hearing loss.

What condition is associated with MYO7A p.Arg88Cys (c.262C>T)?

MYO7A p.Arg88Cys (c.262C>T) is associated with Monogenic hearing loss (ClinVar).

How common is MYO7A p.Arg88Cys (c.262C>T) in the general population?

MYO7A p.Arg88Cys (c.262C>T) is very rare (popmax 0.00118%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg88Cys (c.262C>T)?

AlphaMissense predicts likely pathogenic (score 0.9159) — an in-silico prediction, not a clinical call.

MYO7A p.Arg88Cys

c.262C>T · rs1405840651 · VCV1303902

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9159 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Monogenic hearing loss

Computational evidence

Protein change
AlphaMissense	0.9159	likely pathogenic
REVEL	0.954	strongly pathogenic-leaning
SaProt	LLR -14.06	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 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.00118% South Asian · 1/84,494 alleles

Overall 6.41e-05% 1/1,560,278 alleles · very rare exomes 1/1,408,018 · genomes 0/152,260 · joint denominator

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.Arg88Cys
Coding: c.262C>T
MANE Select: NM_000260
dbSNP: rs1405840651
Type: single nucleotide variant
Location: chr11:77147927 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 88: the myosin motor domain

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

Disease context

Monogenic hearing loss

Similar variants

MYO7A p.Arg88= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Arg88Ser Uncertain significance ★ ⚠ same residue
MYO7A c.133-2A>G Pathogenic ★★ same condition
MYO7A c.1344-2A>G Pathogenic ★★ same condition
MYO7A c.1690+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.18+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.19-1G>A Likely pathogenic ★★ same condition
MYO7A c.2187+1G>A Pathogenic/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-arg88cys (accessed [today's date]).

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