Is MYO7A p.Arg836His (c.2507G>A) pathogenic?

MYO7A p.Arg836His (c.2507G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.1116); Ultra-rare (popmax 0.0151%, afr); Associated with autosomal dominant nonsyndromic hearing loss 11.

How common is MYO7A p.Arg836His (c.2507G>A) in the general population?

MYO7A p.Arg836His (c.2507G>A) is ultra-rare (popmax 0.0151%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg836His (c.2507G>A)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

MYO7A p.Arg836His

Q: What condition is associated with MYO7A p.Arg836His (c.2507G>A)?

MYO7A p.Arg836His (c.2507G>A) is associated with autosomal dominant nonsyndromic hearing loss 11, Meniere disease, Usher syndrome type 1 (ClinVar).

c.2507G>A · rs782179888 · VCV306177

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.6	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 0.0151% African / African-American · 11/73,006 alleles

Filtering AF 0.00836% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00648%

Overall 0.00312% 48/1,540,808 alleles · ultra-rare exomes 41/1,388,580 · genomes 7/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0151%	6,637
South Asian	0.00952%	10,499
Remaining individualsnot grpmax-eligible	0.00501%	19,971
Admixed American	0.00392%	25,493
East Asian	0.00244%	40,910
Finnishnot grpmax-eligible	0.00198%	50,462
European (non-Finnish)	0.00192%	52,126

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.Arg836His
Coding: c.2507G>A
MANE Select: NM_000260
dbSNP: rs782179888
Type: single nucleotide variant
Location: chr11:77179874 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Meniere disease Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 Usher syndrome type 1B

Similar variants

MYO7A p.Arg836Cys Conflicting classifications of pathogenicity ★ ⚠ 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
MYO7A p.Glu968Asp 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-arg836his (accessed [today's date]).

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