Is FERMT1 p.Phe277Val (c.829T>G) pathogenic?

FERMT1 p.Phe277Val (c.829T>G) is classified Uncertain significance in FERMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.381); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FERMT1 p.Phe277Val (c.829T>G)?

FERMT1 p.Phe277Val (c.829T>G) is associated with Inborn genetic diseases (ClinVar).

How common is FERMT1 p.Phe277Val (c.829T>G) in the general population?

FERMT1 p.Phe277Val (c.829T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FERMT1 p.Phe277Val (c.829T>G)?

AlphaMissense predicts ambiguous (score 0.381) — an in-silico prediction, not a clinical call.

FERMT1 p.Phe277Val

c.829T>G · VCV4619847

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.381 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.381	ambiguous
REVEL	0.896	moderately pathogenic-leaning
SaProt	LLR -11.17	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	26.0	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: FERMT1
Protein: p.Phe277Val
Coding: c.829T>G
MANE Select: NM_017671
Type: single nucleotide variant
Location: chr20:6107552 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 277: the ferm domain

Full FERMT1 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

Similar variants

FERMT1 p.Phe277Leu Uncertain significance ★ ⚠ same residue
FERMT1 p.Ala345Val Uncertain significance ★★ ⚠ same condition
FERMT1 p.Ala359Val Uncertain significance ★★ ⚠ same condition
FERMT1 p.Ala539Val Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg108Thr Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg17His Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg255His Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg522Trp Uncertain significance ★★ ⚠ 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/fermt1-p-phe277val (accessed [today's date]).

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