Is MYO7A p.Asp91Gly (c.272A>G) pathogenic?

MYO7A p.Asp91Gly (c.272A>G) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.1551); Absent from gnomAD v4.1.

How common is MYO7A p.Asp91Gly (c.272A>G) in the general population?

MYO7A p.Asp91Gly (c.272A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Asp91Gly (c.272A>G)?

AlphaMissense predicts likely benign (score 0.1551) — an in-silico prediction, not a clinical call.

MYO7A p.Asp91Gly

c.272A>G · rs2135708662 · VCV1498808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1551 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1551	likely benign
REVEL	0.428	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Asp91Gly
Coding: c.272A>G
MANE Select: NM_000260
dbSNP: rs2135708662
Type: single nucleotide variant
Location: chr11:77147937 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 91: the myosin motor domain

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

Similar variants

MYO7A p.Asp91Ala Uncertain significance ★ ⚠ same residue
MYO7A p.Asp91Glu Uncertain significance ★ ⚠ same residue
MYO7A p.Asp91His Uncertain significance ★ ⚠ same residue
MYO7A p.Asp91Tyr Uncertain significance ★ ⚠ same residue
MYO7A p.Asp91fs Likely 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-asp91gly (accessed [today's date]).

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