Is MYO7A p.Glu513Val (c.1538A>T) pathogenic?

MYO7A p.Glu513Val (c.1538A>T) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Glu513Val (c.1538A>T)?

MYO7A p.Glu513Val (c.1538A>T) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Glu513Val (c.1538A>T) in the general population?

MYO7A p.Glu513Val (c.1538A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Glu513Val (c.1538A>T)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

MYO7A p.Glu513Val

c.1538A>T · VCV3601453

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic ✓ concordant with ClinVar · top 6% in MYO7A
REVEL	0.919	moderately pathogenic-leaning
SaProt	LLR -11.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ1.00	donor gain · deltas
Pangolin	Δ0.87	gain · loss 0.85 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 0.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	35.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Glu513Val
Coding: c.1538A>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77162314 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 513: 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.Glu513Gln Likely pathogenic ★ ⚠ same residue
MYO7A p.Glu513Asp 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

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-glu513val (accessed [today's date]).

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