Is MYO7A p.Gly1942Arg (c.5824G>A) pathogenic?

MYO7A p.Gly1942Arg (c.5824G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2025-06-06). AlphaMissense: likely pathogenic (0.9921); Very rare (popmax 0.00664%, sas); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Gly1942Arg (c.5824G>A)?

MYO7A p.Gly1942Arg (c.5824G>A) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Gly1942Arg (c.5824G>A) in the general population?

MYO7A p.Gly1942Arg (c.5824G>A) is very rare (popmax 0.00664%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Gly1942Arg (c.5824G>A)?

AlphaMissense predicts likely pathogenic (score 0.9921) — an in-silico prediction, not a clinical call.

MYO7A p.Gly1942Arg

c.5824G>A · rs111033192 · VCV43299

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.9921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00664%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9921	likely pathogenic
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -15.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	29.2	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 0.00664% South Asian · 6/90,302 alleles

Filtering AF 0.00288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000434% 7/1,611,512 alleles · very rare exomes 7/1,459,262 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00664%	15,050
European (non-Finnish)	8.48e-05%	1,178,888

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.Gly1942Arg
Coding: c.5824G>A
MANE Select: NM_000260
dbSNP: rs111033192
Type: single nucleotide variant
Location: chr11:77207370 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1942: the ferm 2 domain

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

Disease context

MYO7A-related disorder

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

Similar variants

MYO7A p.Gly1942Ter Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.Gly1942= 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-gly1942arg (accessed [today's date]).

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