Is MYO7B p.Ala1967Val (c.5900C>T) pathogenic?

MYO7B p.Ala1967Val (c.5900C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.0808); Ultra-rare (popmax 0.0322%, afr).

How common is MYO7B p.Ala1967Val (c.5900C>T) in the general population?

MYO7B p.Ala1967Val (c.5900C>T) is ultra-rare (popmax 0.0322%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Ala1967Val (c.5900C>T)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

MYO7B p.Ala1967Val

c.5900C>T · rs199543587 · VCV2372753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0322%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -4.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.59	GERP -1.8, phastCons 0.13
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	17.47	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1941V vs ClinVar A1967V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0322% African / African-American · 24/74,534 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00226% 36/1,594,598 alleles · ultra-rare exomes 30/1,442,270 · genomes 6/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0322%	3,106
Remaining individualsnot grpmax-eligible	0.0113%	8,833
South Asian	0.00228%	43,824
European (non-Finnish)	0.000256%	390,271

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: MYO7B
Protein: p.Ala1967Val
Coding: c.5900C>T
MANE Select: NM_001393586
dbSNP: rs199543587
Type: single nucleotide variant
Location: chr2:127635801 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1941 UniProt numbering: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region; an α-helix

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYO7B p.Thr349Met Uncertain significance ★★ ⚠ same type
MYO7B p.Ile1309Val Benign ★★ same type
MYO7B p.Val1556Ile Benign ★★ same type
MYO7B p.Val1876= Benign ★★ same type
MYO7B p.Ala1010Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1092Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1109Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1126Thr Uncertain significance ★ ⚠ 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/myo7b-p-ala1967val (accessed [today's date]).

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