Is MYO7A p.Val1519Met (c.4555G>A) pathogenic?

MYO7A p.Val1519Met (c.4555G>A) is classified Likely benign in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-06). AlphaMissense: likely pathogenic (0.9477); Ultra-rare (popmax 0.0147%, afr); Associated with inherited retinal dystrophy.

What condition is associated with MYO7A p.Val1519Met (c.4555G>A)?

MYO7A p.Val1519Met (c.4555G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is MYO7A p.Val1519Met (c.4555G>A) in the general population?

MYO7A p.Val1519Met (c.4555G>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Val1519Met (c.4555G>A)?

AlphaMissense predicts likely pathogenic (score 0.9477) — an in-silico prediction, not a clinical call.

MYO7A p.Val1519Met

c.4555G>A · rs778449478 · VCV2074119

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9477 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9477	likely pathogenic
REVEL	0.693	pathogenic-leaning
SaProt	LLR -10.82	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 2.9	GERP 0.64, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	28.3	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 0.0147% African / African-American · 11/74,936 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00266% 43/1,613,666 alleles · ultra-rare exomes 30/1,461,450 · genomes 13/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,812
Admixed American	0.00667%	14,997
South Asian	0.00439%	22,765
East Asian	0.00223%	44,894
European (non-Finnish)	0.00186%	53,629
Finnishnot grpmax-eligible	0.00156%	63,902

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.Val1519Met
Coding: c.4555G>A
MANE Select: NM_000260
dbSNP: rs778449478
Type: single nucleotide variant
Location: chr11:77198608 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1519: the ferm 1 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Val1372Gly Likely pathogenic ★★★ same condition
MYO7A p.Arg302His Likely benign ★★★ ⚠ same condition
MYO7A c.2283-1G>T Pathogenic ★★ same condition
MYO7A c.3109-2A>G Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.6439-2A>G 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-val1519met (accessed [today's date]).

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