Is MYO7A p.Phe213= (c.639C>T) pathogenic?

MYO7A p.Phe213= (c.639C>T) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Rare (popmax 0.196%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Phe213= (c.639C>T)?

MYO7A p.Phe213= (c.639C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Phe213= (c.639C>T) in the general population?

MYO7A p.Phe213= (c.639C>T) is rare (popmax 0.196%, eas) (gnomAD).

MYO7A p.Phe213=

c.639C>T · rs540197003 · VCV517430

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.196%, eas)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.9	GERP -3.8
Overall
CADD	3.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.196% East Asian · 88/44,878 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.00911% 147/1,614,020 alleles · rare exomes 124/1,461,680 · genomes 23/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.196%	510
South Asian	0.0428%	2,336
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	60,032
African / African-American	0.00133%	75,056
European (non-Finnish)	0.00127%	78,660

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.Phe213=
Coding: c.639C>T
MANE Select: NM_000260
dbSNP: rs540197003
Type: single nucleotide variant
Location: chr11:77156908 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 213: the myosin motor 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.Phe213Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Phe213Tyr 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-phe213 (accessed [today's date]).

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