Is MYH7 p.Ala26Val (c.77C>T) pathogenic?

MYH7 p.Ala26Val (c.77C>T) is classified Benign in MYH7 (ClinVar, Expert panel, 19 submitters; last evaluated 2025-11-11). AlphaMissense: likely benign (0.2922); Rare (popmax 0.613%, eas); Associated with hypertrophic cardiomyopathy.

What condition is associated with MYH7 p.Ala26Val (c.77C>T)?

MYH7 p.Ala26Val (c.77C>T) is associated with hypertrophic cardiomyopathy, cardiomyopathy, MYH7-related skeletal myopathy (ClinVar).

How common is MYH7 p.Ala26Val (c.77C>T) in the general population?

MYH7 p.Ala26Val (c.77C>T) is rare (popmax 0.613%, eas) (gnomAD).

What do computational predictors say about MYH7 p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.2922) — an in-silico prediction, not a clinical call.

MYH7 p.Ala26Val

c.77C>T · rs186964570 · VCV37375

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 19 submitters

AlphaMissense

likely benign

0.2922 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.613%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hypertrophic cardiomyopathy

ClinGen expert panel — Cardiomyopathy VCEP

Benign for hypertrophic cardiomyopathy. Applied ACMG criteria (verbatim):

BA1

Curation rationale (ClinGen, verbatim)

The filtering allele frequency of the c.77C>T (p.Ala26Val) variant in the MYH7 gene is 0.55% (60/8646) of East Asian chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.2922	likely benign
REVEL	0.573	indeterminate
SaProt	LLR -11.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 527 bp · p 0.58 · regional, not allelic
Overall
CADD	23.4	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 0.613% East Asian · 275/44,888 alleles

Filtering AF 0.553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.53%

Overall 0.0241% 389/1,614,270 alleles · rare exomes 342/1,461,888 · genomes 47/152,382 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.613%	163
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
Remaining individualsnot grpmax-eligible	0.0256%	3,907
South Asian	0.00768%	13,013
Admixed American	0.00666%	15,009
European (non-Finnish)	0.00593%	16,858

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: MYH7
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_000257
dbSNP: rs186964570
Type: single nucleotide variant
Location: chr14:23433656 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.45 · 46 PDB
Residue 26: a UniProt-annotated variant site (in cmh1; benign); an α-helix

Full MYH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: cardiomyopathy MYH7-related skeletal myopathy congenital myopathy 7A, myosin storage, autosomal dominant hypertrophic cardiomyopathy 1 myopathy, myosin storage, autosomal recessive congenital fiber-type disproportion myopathy dilated cardiomyopathy 1S familial hypertrophic cardiomyopathy

Similar variants

MYH7 p.Ala26Thr Uncertain significance ★★ ⚠ same residue
MYH7 p.Ala26= Likely benign ★ same residue
MYH7 p.Arg1045Leu Likely pathogenic ★★★ same condition
MYH7 p.Arg1053Gln Pathogenic ★★★ same condition
MYH7 p.Arg1193His Likely pathogenic ★★★ same condition
MYH7 p.Arg1420Trp Likely pathogenic ★★★ same condition
MYH7 p.Arg143Gln Likely pathogenic ★★★ same condition
MYH7 p.Arg143Trp 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/myh7-p-ala26val (accessed [today's date]).

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