Is MYO7A p.His220Tyr (c.658C>T) pathogenic?

MYO7A p.His220Tyr (c.658C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.2543); Very rare (popmax 0.0039%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.His220Tyr (c.658C>T)?

MYO7A p.His220Tyr (c.658C>T) is associated with Inborn genetic diseases, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.His220Tyr (c.658C>T) in the general population?

MYO7A p.His220Tyr (c.658C>T) is very rare (popmax 0.0039%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.His220Tyr (c.658C>T)?

AlphaMissense predicts likely benign (score 0.2543) — an in-silico prediction, not a clinical call.

MYO7A p.His220Tyr

c.658C>T · rs781857167 · VCV844307

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2543 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2543	likely benign
REVEL	0.717	pathogenic-leaning
SaProt	LLR -5.28	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 2.7	GERP -1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.1	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 0.0039% European (non-Finnish) · 46/1,179,906 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00285% 46/1,613,926 alleles · very rare exomes 42/1,461,674 · genomes 4/152,252 · 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.His220Tyr
Coding: c.658C>T
MANE Select: NM_000260
dbSNP: rs781857167
Type: single nucleotide variant
Location: chr11:77156927 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 220: the myosin motor domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1B

Similar variants

MYO7A p.His220Arg Uncertain significance ★ ⚠ same residue
MYO7A p.His220= 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-his220tyr (accessed [today's date]).

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