Is MYO7A p.Arg1732His (c.5195G>A) pathogenic?

MYO7A p.Arg1732His (c.5195G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-06). AlphaMissense: likely pathogenic (0.6162); Ultra-rare (popmax 0.0176%, amr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg1732His (c.5195G>A)?

MYO7A p.Arg1732His (c.5195G>A) is associated with Inborn genetic diseases, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg1732His (c.5195G>A) in the general population?

MYO7A p.Arg1732His (c.5195G>A) is ultra-rare (popmax 0.0176%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg1732His (c.5195G>A)?

AlphaMissense predicts likely pathogenic (score 0.6162) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1732His

c.5195G>A · rs760544219 · VCV989482

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6162 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6162	likely pathogenic
REVEL	0.523	indeterminate
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt 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 1.8, 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 0.0176% Admixed American · 9/51,000 alleles

Filtering AF 0.00917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00678%

Overall 0.00497% 77/1,548,406 alleles · ultra-rare exomes 74/1,396,168 · genomes 3/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0176%	5,667
South Asian	0.00834%	11,997
Remaining individualsnot grpmax-eligible	0.00501%	19,965
European (non-Finnish)	0.0048%	20,852
African / African-American	0.00274%	36,492
East Asian	0.00244%	40,942

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.Arg1732His
Coding: c.5195G>A
MANE Select: NM_000260
dbSNP: rs760544219
Type: single nucleotide variant
Location: chr11:77203086 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1B

Similar variants

MYO7A p.Arg1732Cys Uncertain significance ★ ⚠ same residue
MYO7A p.Arg1732= 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-arg1732his (accessed [today's date]).

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