Is MYO7A p.Lys515Gln (c.1543A>C) pathogenic?

MYO7A p.Lys515Gln (c.1543A>C) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-25). AlphaMissense: likely pathogenic (0.5942); Rare (popmax 0.173%, sas); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Lys515Gln (c.1543A>C)?

MYO7A p.Lys515Gln (c.1543A>C) 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.Lys515Gln (c.1543A>C) in the general population?

MYO7A p.Lys515Gln (c.1543A>C) is rare (popmax 0.173%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Lys515Gln (c.1543A>C)?

AlphaMissense predicts likely pathogenic (score 0.5942) — an in-silico prediction, not a clinical call.

MYO7A p.Lys515Gln

c.1543A>C · rs782023308 · VCV179865

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.5942 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.173%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.5942	likely pathogenic
REVEL	0.417	indeterminate
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -0.43, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.9	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 0.173% South Asian · 145/84,032 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.00992% 154/1,551,642 alleles · rare exomes 148/1,399,330 · genomes 6/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.173%	580
Middle Eastern	0.0513%	1,948
Remaining individualsnot grpmax-eligible	0.00998%	10,019

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.Lys515Gln
Coding: c.1543A>C
MANE Select: NM_000260
dbSNP: rs782023308
Type: single nucleotide variant
Location: chr11:77162319 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 515: 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

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

Similar variants

MYO7A p.Lys515Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Lys515= 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-lys515gln (accessed [today's date]).

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