Is FAP p.Gly348Ser (c.1042G>A) pathogenic?

FAP p.Gly348Ser (c.1042G>A) is classified Uncertain significance in FAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: ambiguous (0.407); Very rare (popmax 0.00167%, amr).

How common is FAP p.Gly348Ser (c.1042G>A) in the general population?

FAP p.Gly348Ser (c.1042G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FAP p.Gly348Ser (c.1042G>A)?

AlphaMissense predicts ambiguous (score 0.407) — an in-silico prediction, not a clinical call.

FAP p.Gly348Ser

c.1042G>A · VCV3513019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.407 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.407	ambiguous
REVEL	0.578	indeterminate
SaProt	LLR -5.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.75 · regional, not allelic
Overall
CADD	28.5	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

Grpmax group 0.00167% Admixed American · 1/59,988 alleles

Overall 0.000124% 2/1,612,574 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,420

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: FAP
Protein: p.Gly348Ser
Coding: c.1042G>A
MANE Select: NM_004460
Type: single nucleotide variant
Location: chr2:162209957 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.72 · 4 PDB
Residue 348: a β-strand

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

Similar variants

FAP c.1870-8C>A Benign ★★ same type
FAP p.Ala100= Benign ★★ same type
FAP p.Gln708= Benign ★★ same type
FAP p.Gly195= Benign ★★ same type
FAP p.Leu212Phe Benign ★★ ⚠ same type
FAP p.Phe185Leu Likely benign ★★ ⚠ same type
FAP p.Ser737= Likely benign ★★ same type
FAP p.Thr229Met Benign ★★ ⚠ 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/fap-p-gly348ser (accessed [today's date]).

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