Is MYO7A p.Arg1790His (c.5369G>A) pathogenic?

MYO7A p.Arg1790His (c.5369G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-06). AlphaMissense: likely benign (0.2809); Very rare (popmax 0.00453%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg1790His (c.5369G>A)?

MYO7A p.Arg1790His (c.5369G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg1790His (c.5369G>A) in the general population?

MYO7A p.Arg1790His (c.5369G>A) is very rare (popmax 0.00453%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg1790His (c.5369G>A)?

AlphaMissense predicts likely benign (score 0.2809) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1790His

c.5369G>A · rs372016012 · VCV840818

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00453%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.2809	likely benign
REVEL	0.689	pathogenic-leaning
SaProt	LLR -5.15	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.0	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 0.00453% East Asian · 2/44,104 alleles

Filtering AF 0.000752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000541%

Overall 0.00119% 19/1,600,540 alleles · very rare exomes 16/1,448,338 · genomes 3/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00453%	22,052
Admixed American	0.00171%	58,390
African / African-American	0.00134%	74,522
European (non-Finnish)	0.00119%	83,849
South Asian	0.00113%	88,184

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.Arg1790His
Coding: c.5369G>A
MANE Select: NM_000260
dbSNP: rs372016012
Type: single nucleotide variant
Location: chr11:77204118 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1790: the myth4 2 domain

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

Disease context

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

Similar variants

MYO7A p.Arg1790Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg1790Ser Uncertain significance ★ ⚠ 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-arg1790his (accessed [today's date]).

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