Is MYO7A p.Gly1982Glu (c.5945G>A) pathogenic?

MYO7A p.Gly1982Glu (c.5945G>A) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2020-05-15). AlphaMissense: ambiguous (0.3742); Very rare (popmax 0.00233%, eas); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Gly1982Glu (c.5945G>A)?

MYO7A p.Gly1982Glu (c.5945G>A) is associated with MYO7A-related disorder (ClinVar).

How common is MYO7A p.Gly1982Glu (c.5945G>A) in the general population?

MYO7A p.Gly1982Glu (c.5945G>A) is very rare (popmax 0.00233%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Gly1982Glu (c.5945G>A)?

AlphaMissense predicts ambiguous (score 0.3742) — an in-silico prediction, not a clinical call.

MYO7A p.Gly1982Glu

c.5945G>A · rs111033250 · VCV43310

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3742 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00233%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.3742	ambiguous
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.27	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.40	loss · gain 0.30 · agrees with SpliceAI · independent
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	30.0	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 0.00233% East Asian · 1/42,932 alleles

Overall 6.33e-05% 1/1,578,974 alleles · very rare exomes 0/1,426,822 · genomes 1/152,152 · 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.Gly1982Glu
Coding: c.5945G>A
MANE Select: NM_000260
dbSNP: rs111033250
Type: single nucleotide variant
Location: chr11:77208697 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1982: the ferm 2 domain

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

Disease context

MYO7A-related disorder

Similar variants

MYO7A p.Gly1982Arg Pathogenic/Likely pathogenic ★★ ⚠ same residue
MYO7A p.Gly1982= Likely benign ★ same residue
MYO7A c.133-2A>G Pathogenic ★★ same condition
MYO7A c.1344-2A>G Pathogenic ★★ same condition
MYO7A c.1690+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.18+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.19-1G>A Likely pathogenic ★★ same condition
MYO7A c.2187+1G>A Pathogenic/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-gly1982glu (accessed [today's date]).

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