Is MYO7A p.Phe1297Leu (c.3891C>G) pathogenic?

MYO7A p.Phe1297Leu (c.3891C>G) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2023-10-03). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1; Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Phe1297Leu (c.3891C>G)?

MYO7A p.Phe1297Leu (c.3891C>G) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Phe1297Leu (c.3891C>G) in the general population?

MYO7A p.Phe1297Leu (c.3891C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYO7A p.Phe1297Leu (c.3891C>G)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

MYO7A p.Phe1297Leu

c.3891C>G · rs375475374 · VCV1462559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic · top 8% in MYO7A
REVEL	0.537	indeterminate
SaProt	LLR -9.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.5	GERP -3.5
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	14.71	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Phe1297Leu
Coding: c.3891C>G
MANE Select: NM_000260
dbSNP: rs375475374
Type: single nucleotide variant
Location: chr11:77190837 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1297: the ferm 1 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.Phe1297Tyr Uncertain significance ⚠ same residue
MYO7A p.Phe1297= 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-phe1297leu (accessed [today's date]).

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