Is MYO7A p.Phe213Leu (c.639C>G) pathogenic?

MYO7A p.Phe213Leu (c.639C>G) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2020-01-10). AlphaMissense: likely pathogenic (0.9991); Very rare (popmax 8.48e-05%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Phe213Leu (c.639C>G)?

MYO7A p.Phe213Leu (c.639C>G) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Phe213Leu (c.639C>G) in the general population?

MYO7A p.Phe213Leu (c.639C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Phe213Leu (c.639C>G)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

MYO7A p.Phe213Leu

c.639C>G · rs540197003 · VCV1018688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9991 · 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 1B

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic · top 1% in MYO7A
REVEL	0.665	pathogenic-leaning
SaProt	LLR -12.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.9	GERP -3.8
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	13.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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) · 1/1,179,904 alleles

Overall 6.2e-05% 1/1,614,020 alleles · very rare exomes 1/1,461,680 · genomes 0/152,340 · 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.Phe213Leu
Coding: c.639C>G
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.Phe213= Benign/Likely benign ★★ 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-phe213leu (accessed [today's date]).

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