Is MYO7B p.Ala2093Val (c.6278C>T) pathogenic?

MYO7B p.Ala2093Val (c.6278C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely benign (0.0742); Rare (popmax 0.148%, mid); Associated with neuromuscular disease.

What condition is associated with MYO7B p.Ala2093Val (c.6278C>T)?

MYO7B p.Ala2093Val (c.6278C>T) is associated with neuromuscular disease (ClinVar).

How common is MYO7B p.Ala2093Val (c.6278C>T) in the general population?

MYO7B p.Ala2093Val (c.6278C>T) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about MYO7B p.Ala2093Val (c.6278C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

MYO7B p.Ala2093Val

c.6278C>T · VCV3383284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuromuscular disease

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -3.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -3.8
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	0.132	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 A2067V vs ClinVar A2093V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0975% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0901%

Overall 0.0301% 485/1,613,390 alleles · rare exomes 407/1,461,214 · genomes 78/152,176 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
African / African-American	0.117%	853
Remaining individualsnot grpmax-eligible	0.0672%	1,487
European (non-Finnish)	0.0273%	3,664
Admixed American	0.0233%	4,287
South Asian	0.00988%	10,119
East Asian	0.00223%	44,830

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.Ala2093Val
Coding: c.6278C>T
MANE Select: NM_001393586
Type: single nucleotide variant
Location: chr2:127636864 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 2067 UniProt numbering: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region; a β-strand

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

Disease context

neuromuscular disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7B p.Ala2093Thr Uncertain significance ★ ⚠ same residue
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

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-ala2093val (accessed [today's date]).

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