Is FAT2 p.Arg3777Ser (c.11331G>T) pathogenic?

FAT2 p.Arg3777Ser (c.11331G>T) is classified Uncertain significance in FAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.2266); Very rare (popmax 0.00446%, eas).

How common is FAT2 p.Arg3777Ser (c.11331G>T) in the general population?

FAT2 p.Arg3777Ser (c.11331G>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about FAT2 p.Arg3777Ser (c.11331G>T)?

AlphaMissense predicts likely benign (score 0.2266) — an in-silico prediction, not a clinical call.

FAT2 p.Arg3777Ser

c.11331G>T · rs1753012109 · VCV3093097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2266	likely benign
REVEL	0.07	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 1.8	GERP -0.28, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 2.4e-06 · regional, not allelic
Overall
CADD	17.85	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

Grpmax group 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,160 alleles · very rare exomes 2/1,461,870 · genomes 0/152,290 · 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: FAT2
Protein: p.Arg3777Ser
Coding: c.11331G>T
MANE Select: NM_001447
dbSNP: rs1753012109
Type: single nucleotide variant
Location: chr5:151517752 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI <0.01 (gnomAD)
Residue 3777: the laminin g-like domain

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

Similar variants

FAT2 p.Arg3777Thr Uncertain significance ★ ⚠ same residue
FAT2 p.Arg3777= Likely benign ★ same residue
FAT2 p.Arg3777Lys Uncertain significance ⚠ same residue
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

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-arg3777ser (accessed [today's date]).

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