Is MYO7A p.Ala1340= (c.4020C>T) pathogenic?

MYO7A p.Ala1340= (c.4020C>T) is classified Likely benign in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-23). Very rare (popmax 0.00329%, sas).

How common is MYO7A p.Ala1340= (c.4020C>T) in the general population?

MYO7A p.Ala1340= (c.4020C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

MYO7A p.Ala1340=

c.4020C>T · rs771609333 · VCV1563503

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.6	GERP -3.1
Overall
CADD	13.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,090 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,613,994 alleles · very rare exomes 3/1,461,604 · genomes 0/152,390 · joint denominator

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.Ala1340=
Coding: c.4020C>T
MANE Select: NM_000260
dbSNP: rs771609333
Type: single nucleotide variant
Location: chr11:77192146 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1340: the ferm 1 domain

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

Similar variants

MYO7A p.Ala1340Ser Uncertain significance ★★ same residue
MYO7A p.Ala1340Val Uncertain significance ★★ ⚠ same residue
MYO7A p.Ala1340Pro Likely pathogenic ★ ⚠ same residue
MYO7A p.Ala1340Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Ala1340fs Pathogenic ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln 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-ala1340 (accessed [today's date]).

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