Is MYO7A p.Arg90Gln (c.269G>A) pathogenic?

MYO7A p.Arg90Gln (c.269G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-10). AlphaMissense: likely benign (0.0799); Very rare (popmax 0.00136%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg90Gln (c.269G>A)?

MYO7A p.Arg90Gln (c.269G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Arg90Gln (c.269G>A) in the general population?

MYO7A p.Arg90Gln (c.269G>A) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg90Gln (c.269G>A)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

MYO7A p.Arg90Gln

c.269G>A · rs1165878942 · VCV2491140

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -7.29	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 6.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.00136% African / African-American · 1/73,342 alleles

Overall 0.000193% 3/1,555,600 alleles · very rare exomes 3/1,403,442 · genomes 0/152,158 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00166%	60,374
African / African-Americangrpmax	0.00136%	73,342
European (non-Finnish)	8.69e-05%	1,150,575

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg90Gln
Coding: c.269G>A
MANE Select: NM_000260
dbSNP: rs1165878942
Type: single nucleotide variant
Location: chr11:77147934 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 90: the myosin motor domain; a UniProt-annotated variant site (in ush1b)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg90Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr Uncertain significance ★★ ⚠ 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-arg90gln (accessed [today's date]).

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