Is MYO7A p.Ala2039Val (c.6116C>T) pathogenic?

MYO7A p.Ala2039Val (c.6116C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-01). AlphaMissense: likely pathogenic (0.8263); Very rare (popmax 0.00268%, afr).

How common is MYO7A p.Ala2039Val (c.6116C>T) in the general population?

MYO7A p.Ala2039Val (c.6116C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Ala2039Val (c.6116C>T)?

AlphaMissense predicts likely pathogenic (score 0.8263) — an in-silico prediction, not a clinical call.

MYO7A p.Ala2039Val

c.6116C>T · VCV3624721

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8263	likely pathogenic
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -12.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 0.66, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,632 alleles

Filtering AF 0.000695% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000543%

Overall 0.00119% 19/1,591,500 alleles · very rare exomes 17/1,439,236 · genomes 2/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,316
East Asian	0.00228%	43,794
Remaining individualsnot grpmax-eligible	0.00162%	61,672
European (non-Finnish)	0.0012%	83,525
South Asian	0.00115%	86,806

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.Ala2039Val
Coding: c.6116C>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77211216 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2039: the ferm 2 domain; an α-helix

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

Similar variants

MYO7A p.Ala2039= Likely benign ★★ same residue
MYO7A p.Ala2039Ser Uncertain significance ★ ⚠ same residue
MYO7A p.Ala2039Met Uncertain significance ★ 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

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-ala2039val (accessed [today's date]).

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