Is FAP p.Arg426Gly (c.1276A>G) pathogenic?

FAP p.Arg426Gly (c.1276A>G) is classified Uncertain significance in FAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: ambiguous (0.5053); Very rare (popmax 0.00177%, nfe).

How common is FAP p.Arg426Gly (c.1276A>G) in the general population?

FAP p.Arg426Gly (c.1276A>G) is very rare (popmax 0.00177%, nfe) (gnomAD).

What do computational predictors say about FAP p.Arg426Gly (c.1276A>G)?

AlphaMissense predicts ambiguous (score 0.5053) — an in-silico prediction, not a clinical call.

FAP p.Arg426Gly

c.1276A>G · rs758981922 · VCV2323350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5053	ambiguous
REVEL	0.615	indeterminate
SaProt	LLR -10.89	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.75 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.00177% European (non-Finnish) · 19/1,074,828 alleles

Filtering AF 0.00113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000911%

Overall 0.00136% 20/1,475,990 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00177%	56,570
Remaining individualsnot grpmax-eligible	0.00174%	57,414

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.Arg426Gly
Coding: c.1276A>G
MANE Select: NM_004460
dbSNP: rs758981922
Type: single nucleotide variant
Location: chr2:162200567 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.72 · 4 PDB
Residue 426: 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-arg426gly (accessed [today's date]).

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