Is MYO7A p.Val1319Ile (c.3955G>A) pathogenic?

MYO7A p.Val1319Ile (c.3955G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-09-12). AlphaMissense: likely benign (0.1212); Ultra-rare (popmax 0.0559%, afr).

How common is MYO7A p.Val1319Ile (c.3955G>A) in the general population?

MYO7A p.Val1319Ile (c.3955G>A) is ultra-rare (popmax 0.0559%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Val1319Ile (c.3955G>A)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

MYO7A p.Val1319Ile

c.3955G>A · rs200483708 · VCV1106322

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0559%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.0559% African / African-American · 42/75,080 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00799% 129/1,613,738 alleles · ultra-rare exomes 100/1,461,376 · genomes 29/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0559%	1,788
Middle Eastern	0.0166%	6,016
European (non-Finnish)	0.00653%	15,323
Remaining individualsnot grpmax-eligible	0.0064%	15,619
South Asian	0.00439%	22,769
Admixed American	0.00167%	60,016

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.Val1319Ile
Coding: c.3955G>A
MANE Select: NM_000260
dbSNP: rs200483708
Type: single nucleotide variant
Location: chr11:77192081 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1319: the ferm 1 domain

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

Similar variants

MYO7A p.Val1319Ala Uncertain significance ★★ ⚠ same residue
MYO7A p.Val1319= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His Likely pathogenic ★★★ same type

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-val1319ile (accessed [today's date]).

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