Is MYO7A p.Arg1832Gln (c.5495G>A) pathogenic?

MYO7A p.Arg1832Gln (c.5495G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-09-01). AlphaMissense: likely benign (0.2628); Ultra-rare (popmax 0.0932%, afr); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Arg1832Gln (c.5495G>A)?

MYO7A p.Arg1832Gln (c.5495G>A) is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg1832Gln (c.5495G>A) in the general population?

MYO7A p.Arg1832Gln (c.5495G>A) is ultra-rare (popmax 0.0932%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg1832Gln (c.5495G>A)?

AlphaMissense predicts likely benign (score 0.2628) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1832Gln

c.5495G>A · rs372768607 · VCV178494

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0932%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.2628	likely benign
REVEL	0.662	pathogenic-leaning
SaProt	LLR -8.78	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	28.5	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 0.0932% African / African-American · 69/74,028 alleles

Filtering AF 0.0755% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0691%

Overall 0.00621% 98/1,578,034 alleles · ultra-rare exomes 60/1,425,738 · genomes 38/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0932%	1,073
Admixed American	0.00731%	13,687
East Asian	0.00706%	14,171
Remaining individualsnot grpmax-eligible	0.00654%	15,285
South Asian	0.00349%	28,657
European (non-Finnish)	0.00129%	77,508

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.Arg1832Gln
Coding: c.5495G>A
MANE Select: NM_000260
dbSNP: rs372768607
Type: single nucleotide variant
Location: chr11:77205476 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1832: the myth4 2 domain; an α-helix

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: Usher syndrome type 1B

Similar variants

MYO7A p.Arg1832Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg1832= 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-arg1832gln (accessed [today's date]).

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