Is MYO7A p.Glu380Lys (c.1138G>A) pathogenic?

MYO7A p.Glu380Lys (c.1138G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-10). AlphaMissense: likely pathogenic (0.9892); Very rare (popmax 0.000859%, nfe); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Glu380Lys (c.1138G>A)?

MYO7A p.Glu380Lys (c.1138G>A) is associated with Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Glu380Lys (c.1138G>A) in the general population?

MYO7A p.Glu380Lys (c.1138G>A) is very rare (popmax 0.000859%, nfe) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Glu380Lys (c.1138G>A)?

AlphaMissense predicts likely pathogenic (score 0.9892) — an in-silico prediction, not a clinical call.

MYO7A p.Glu380Lys

c.1138G>A · rs876657913 · VCV228998

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000859%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9892	likely pathogenic
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -10.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.9	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

Grpmax group 0.000859% European (non-Finnish) · 10/1,164,724 alleles

Filtering AF 0.000434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000317%

Overall 0.000632% 10/1,582,098 alleles · very rare exomes 10/1,429,776 · genomes 0/152,322 · 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.Glu380Lys
Coding: c.1138G>A
MANE Select: NM_000260
dbSNP: rs876657913
Type: single nucleotide variant
Location: chr11:77160220 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 380: the myosin motor domain

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Glu380= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely 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/myo7a-p-glu380lys (accessed [today's date]).

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