Is MYO7A p.Arg920Gln (c.2759G>A) pathogenic?

MYO7A p.Arg920Gln (c.2759G>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.00341%, amr).

How common is MYO7A p.Arg920Gln (c.2759G>A) in the general population?

MYO7A p.Arg920Gln (c.2759G>A) is very rare (popmax 0.00341%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg920Gln (c.2759G>A)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

MYO7A p.Arg920Gln

c.2759G>A · rs565162134 · VCV306180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00341%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.509	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 12	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

Grpmax group 0.00341% Admixed American · 2/58,622 alleles

Filtering AF 0.000691% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00054%

Overall 0.00137% 22/1,605,166 alleles · very rare exomes 19/1,452,804 · genomes 3/152,362 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00341%	29,311
African / African-American	0.00267%	37,478
East Asian	0.00224%	44,574
South Asian	0.00224%	44,742
Remaining individualsnot grpmax-eligible	0.00161%	62,196
European (non-Finnish)	0.00119%	84,024

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.Arg920Gln
Coding: c.2759G>A
MANE Select: NM_000260
dbSNP: rs565162134
Type: single nucleotide variant
Location: chr11:77181444 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 920: the 'sah' region

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

Similar variants

MYO7A p.Arg920Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg920Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Arg920Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg920= Likely benign ★ 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

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-arg920gln (accessed [today's date]).

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