Is MYO7A p.Arg1602Gln (c.4805G>A) pathogenic?

MYO7A p.Arg1602Gln (c.4805G>A) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). AlphaMissense: ambiguous (0.4438); Low-frequency (popmax 3.31%, eas); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg1602Gln (c.4805G>A)?

MYO7A p.Arg1602Gln (c.4805G>A) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg1602Gln (c.4805G>A) in the general population?

MYO7A p.Arg1602Gln (c.4805G>A) is low-frequency (popmax 3.31%, eas) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Arg1602Gln (c.4805G>A)?

AlphaMissense predicts ambiguous (score 0.4438) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1602Gln

c.4805G>A · rs139889944 · VCV43260

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

ambiguous

0.4438 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.31%, eas)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.4438	ambiguous
REVEL	0.482	indeterminate
SaProt	LLR -8.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.48, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	28.3	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 3.31% East Asian · 1,481/44,784 alleles

Filtering AF 3.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.11%

Overall 0.111% 1,787/1,611,594 alleles · low-frequency exomes 1,528/1,459,294 · genomes 259/152,300 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	3.31%	30
Remaining individualsnot grpmax-eligible	0.25%	400
South Asian	0.0726%	1,377
Middle Eastern	0.033%	3,027
Admixed American	0.025%	3,995
European (non-Finnish)	0.00543%	18,410
African / African-American	0.004%	25,009

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.Arg1602Gln
Coding: c.4805G>A
MANE Select: NM_000260
dbSNP: rs139889944
Type: single nucleotide variant
Location: chr11:77199771 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1602: the ferm 1 domain; a UniProt-annotated variant site (in ush1b; atypical)

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Arg1602Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg1602= 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-arg1602gln (accessed [today's date]).

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