Is MYO7A p.Ser1196Cys (c.3587C>G) pathogenic?

MYO7A p.Ser1196Cys (c.3587C>G) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-25). AlphaMissense: likely benign (0.3032); Very rare (popmax 0.00439%, sas); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Ser1196Cys (c.3587C>G)?

MYO7A p.Ser1196Cys (c.3587C>G) is associated with autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Ser1196Cys (c.3587C>G) in the general population?

MYO7A p.Ser1196Cys (c.3587C>G) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Ser1196Cys (c.3587C>G)?

AlphaMissense predicts likely benign (score 0.3032) — an in-silico prediction, not a clinical call.

MYO7A p.Ser1196Cys

c.3587C>G · rs1555090376 · VCV3233328

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3032 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.3032	likely benign
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -8.47	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.66, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.4	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 0.00439% South Asian · 4/91,084 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,613,826 alleles · very rare exomes 3/1,461,616 · genomes 1/152,210 · 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.Ser1196Cys
Coding: c.3587C>G
MANE Select: NM_000260
dbSNP: rs1555090376
Type: single nucleotide variant
Location: chr11:77189427 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1196: the myth4 1 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

Similar variants

MYO7A p.Ser1196Phe Uncertain significance ★ ⚠ same residue
MYO7A p.Ser1196Tyr Uncertain significance ★ ⚠ same residue
MYO7A p.Ser1196= Likely benign ★ same residue
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-ser1196cys (accessed [today's date]).

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