Is FAT2 p.Ala4Val (c.11C>T) pathogenic?

FAT2 p.Ala4Val (c.11C>T) is classified Uncertain significance in FAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.075); Absent from gnomAD v4.1.

How common is FAT2 p.Ala4Val (c.11C>T) in the general population?

FAT2 p.Ala4Val (c.11C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAT2 p.Ala4Val (c.11C>T)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

FAT2 p.Ala4Val

c.11C>T · VCV4667133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.12, phastCons 0.98
Regional constraint	o/e 0.90	unconstrained · MANE · 28 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	14.08	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: FAT2
Protein: p.Ala4Val
Coding: c.11C>T
MANE Select: NM_001447
Type: single nucleotide variant
Location: chr5:151568921 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)

Full FAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAT2 p.Ala1009Val Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1078Thr Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1079Asp Uncertain significance ★★ ⚠ same type
FAT2 p.Ala1975Glu Uncertain significance ★★ same type
FAT2 p.Ala2491Glu Uncertain significance ★★ same type
FAT2 p.Ala249Val Uncertain significance ★★ ⚠ same type
FAT2 p.Ala2587Val Uncertain significance ★★ same type
FAT2 p.Ala2618Thr Uncertain significance ★★ same type

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/fat2-p-ala4val (accessed [today's date]).

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