Is MYO7A p.Arg830His (c.2489G>A) pathogenic?

MYO7A p.Arg830His (c.2489G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2025-12-19). AlphaMissense: ambiguous (0.369); Rare (popmax 0.166%, mid); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg830His (c.2489G>A)?

MYO7A p.Arg830His (c.2489G>A) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg830His (c.2489G>A) in the general population?

MYO7A p.Arg830His (c.2489G>A) is rare (popmax 0.166%, mid) (gnomAD).

What do computational predictors say about MYO7A p.Arg830His (c.2489G>A)?

AlphaMissense predicts ambiguous (score 0.369) — an in-silico prediction, not a clinical call.

MYO7A p.Arg830His

c.2489G>A · rs371029653 · VCV191024

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

ambiguous

0.369 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.166%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.369	ambiguous
REVEL	0.763	pathogenic-leaning
SaProt	LLR -9.76	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.32	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.166% Middle Eastern · 9/5,420 alleles

Filtering AF 0.0866% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0646%

Overall 0.00863% 133/1,541,754 alleles · rare exomes 124/1,389,510 · genomes 9/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.166%	602
Remaining individualsnot grpmax-eligible	0.0217%	4,611
Ashkenazi Jewishnot grpmax-eligible	0.014%	7,159
European (non-Finnish)	0.00837%	11,946
East Asian	0.00733%	13,644
South Asian	0.00476%	21,003
African / African-American	0.00411%	24,343
Admixed American	0.00196%	50,988

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.Arg830His
Coding: c.2489G>A
MANE Select: NM_000260
dbSNP: rs371029653
Type: single nucleotide variant
Location: chr11:77179856 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 830: the iq 4 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Arg830Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg830Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Arg830Ser Uncertain significance ★ ⚠ 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

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-arg830his (accessed [today's date]).

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