Is MYO7A p.Ser349Tyr (c.1046C>A) pathogenic?

MYO7A p.Ser349Tyr (c.1046C>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-08-15). AlphaMissense: likely benign (0.3042); Very rare (popmax 0.00683%, amr); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Ser349Tyr (c.1046C>A)?

MYO7A p.Ser349Tyr (c.1046C>A) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ser349Tyr (c.1046C>A) in the general population?

MYO7A p.Ser349Tyr (c.1046C>A) is very rare (popmax 0.00683%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Ser349Tyr (c.1046C>A)?

AlphaMissense predicts likely benign (score 0.3042) — an in-silico prediction, not a clinical call.

MYO7A p.Ser349Tyr

c.1046C>A · rs782432573 · VCV802703

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00683%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.3042	likely benign
REVEL	0.584	indeterminate
SaProt	LLR -13.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.4	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 0.00683% Admixed American · 4/58,602 alleles

Filtering AF 0.00229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000253% 4/1,579,020 alleles · very rare exomes 3/1,429,354 · genomes 1/149,666 · 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.Ser349Tyr
Coding: c.1046C>A
MANE Select: NM_000260
dbSNP: rs782432573
Type: single nucleotide variant
Location: chr11:77159489 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 349: the myosin motor 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

Similar variants

MYO7A p.Ser349Cys Uncertain significance ★★ ⚠ 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
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Gly2187Asp 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-ser349tyr (accessed [today's date]).

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