Is FAP p.Ala211Val (c.632C>T) pathogenic?

FAP p.Ala211Val (c.632C>T) is classified Uncertain significance in FAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: ambiguous (0.5169); Very rare (popmax 0.00403%, afr).

How common is FAP p.Ala211Val (c.632C>T) in the general population?

FAP p.Ala211Val (c.632C>T) is very rare (popmax 0.00403%, afr) (gnomAD).

What do computational predictors say about FAP p.Ala211Val (c.632C>T)?

AlphaMissense predicts ambiguous (score 0.5169) — an in-silico prediction, not a clinical call.

FAP p.Ala211Val

c.632C>T · VCV3277690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5169 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00403%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5169	ambiguous
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -8.71	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.75 · regional, not allelic
Overall
CADD	24.1	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 0.00403% African / African-American · 3/74,380 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000497%

Overall 0.000935% 15/1,604,450 alleles · very rare exomes 10/1,452,420 · genomes 5/152,030 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00403%	24,793
European (non-Finnish)	0.00102%	97,969

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.Ala211Val
Coding: c.632C>T
MANE Select: NM_004460
Type: single nucleotide variant
Location: chr2:162218116 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.72 · 4 PDB

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-ala211val (accessed [today's date]).

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