Is MYO7A p.Arg873Gln (c.2618G>A) pathogenic?

MYO7A p.Arg873Gln (c.2618G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.2674); Ultra-rare (popmax 0.0451%, amr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg873Gln (c.2618G>A)?

MYO7A p.Arg873Gln (c.2618G>A) is associated with Inborn genetic diseases, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg873Gln (c.2618G>A) in the general population?

MYO7A p.Arg873Gln (c.2618G>A) is ultra-rare (popmax 0.0451%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg873Gln (c.2618G>A)?

AlphaMissense predicts likely benign (score 0.2674) — an in-silico prediction, not a clinical call.

MYO7A p.Arg873Gln

c.2618G>A · rs1052032 · VCV43189

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0451%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2674	likely benign
REVEL	0.567	indeterminate
SaProt	LLR -11.82	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	25.7	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 0.0451% Admixed American · 27/59,908 alleles

Filtering AF 0.0318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.0031% 50/1,612,024 alleles · ultra-rare exomes 45/1,459,736 · genomes 5/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0451%	2,219
African / African-American	0.004%	25,013
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.00153%	65,533
South Asian	0.0011%	90,914

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.Arg873Gln
Coding: c.2618G>A
MANE Select: NM_000260
dbSNP: rs1052032
Type: single nucleotide variant
Location: chr11:77180405 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 873: the 'sah' region

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

Similar variants

MYO7A p.Arg873Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg873= 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

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-arg873gln (accessed [today's date]).

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