Is MYO7A p.His133Asp (c.397C>G) pathogenic?

MYO7A p.His133Asp (c.397C>G) is classified Pathogenic in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-06). AlphaMissense: likely pathogenic (0.9629); Very rare (popmax 8.48e-05%, nfe); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.His133Asp (c.397C>G)?

MYO7A p.His133Asp (c.397C>G) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.His133Asp (c.397C>G) in the general population?

MYO7A p.His133Asp (c.397C>G) is very rare (popmax 8.48e-05%, nfe) (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.His133Asp (c.397C>G)?

AlphaMissense predicts likely pathogenic (score 0.9629) — an in-silico prediction, not a clinical call.

MYO7A p.His133Asp

c.397C>G · rs111033403 · VCV552051

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9629	likely pathogenic ✓ concordant with ClinVar
REVEL	0.987	strongly pathogenic-leaning
SaProt	LLR -13.33	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	29.3	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 8.48e-05% European (non-Finnish) · 1/1,179,888 alleles

Overall 6.2e-05% 1/1,613,960 alleles · very rare exomes 1/1,461,582 · genomes 0/152,378 · joint denominator

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.His133Asp
Coding: c.397C>G
MANE Select: NM_000260
dbSNP: rs111033403
Type: single nucleotide variant
Location: chr11:77156018 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 133: the myosin motor domain; a UniProt-annotated variant site (in ush1b; uncertain significance)

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

For Usher syndrome (Orphanet):

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

Similar variants

MYO7A p.His133Asn Likely pathogenic ★★★ same residue
MYO7A p.His133Tyr Pathogenic/Likely pathogenic ★★ same residue
MYO7A p.His133fs Pathogenic ★★ same residue
MYO7A p.His133Gln Likely pathogenic ★ same residue
MYO7A p.His133Pro Uncertain significance ★ ⚠ same residue
MYO7A p.His133= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln 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-his133asp (accessed [today's date]).

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