Is MYO7A p.Glu1327Asp (c.3981G>C) pathogenic?

MYO7A p.Glu1327Asp (c.3981G>C) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1.

How common is MYO7A p.Glu1327Asp (c.3981G>C) in the general population?

MYO7A p.Glu1327Asp (c.3981G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Glu1327Asp (c.3981G>C)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

MYO7A p.Glu1327Asp

c.3981G>C · rs2135575577 · VCV1487928

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic ✓ concordant with ClinVar · top 1% in MYO7A
REVEL	0.616	indeterminate
SaProt	LLR -10.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.27	GERP -0.62, phastCons 0.94
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	21.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Glu1327Asp
Coding: c.3981G>C
MANE Select: NM_000260
dbSNP: rs2135575577
Type: single nucleotide variant
Location: chr11:77192107 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1327: a UniProt-annotated variant site (in ush1b); the ferm 1 domain

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

Similar variants

MYO7A p.Glu1327Lys Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Glu1327Gln Likely pathogenic ★ 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
MYO7A p.Arg853His Likely 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-glu1327asp (accessed [today's date]).

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