Is MYO7A p.Arg1883Gln (c.5648G>A) pathogenic?

MYO7A p.Arg1883Gln (c.5648G>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 15 submitters; last evaluated 2025-12-27). AlphaMissense: likely pathogenic (0.9888); Ultra-rare (popmax 0.01%, amr); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Arg1883Gln (c.5648G>A)?

MYO7A p.Arg1883Gln (c.5648G>A) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg1883Gln (c.5648G>A) in the general population?

MYO7A p.Arg1883Gln (c.5648G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg1883Gln (c.5648G>A)?

AlphaMissense predicts likely pathogenic (score 0.9888) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1883Gln

c.5648G>A · rs111033215 · VCV43294

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

AlphaMissense

likely pathogenic

0.9888 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7A-related disorder

Computational evidence

Protein change
AlphaMissense	0.9888	likely pathogenic ✓ concordant with ClinVar
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -14.56	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 10	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	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 0.01% Admixed American · 6/59,838 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00192% 31/1,612,222 alleles · ultra-rare exomes 25/1,460,026 · genomes 6/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,973
African / African-American	0.004%	24,981
East Asian	0.00223%	44,800
European (non-Finnish)	0.0017%	58,964
South Asian	0.0011%	90,586

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.Arg1883Gln
Coding: c.5648G>A
MANE Select: NM_000260
dbSNP: rs111033215
Type: single nucleotide variant
Location: chr11:77206108 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1883: the myth4 2 domain; a UniProt-annotated variant site (in ush1b)

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 inherited retinal dystrophy Usher syndrome Usher syndrome type 1B

Similar variants

MYO7A p.Arg1883Trp Pathogenic/Likely pathogenic ★★ 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-arg1883gln (accessed [today's date]).

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