Is FAP p.Leu212Phe (c.634C>T) pathogenic?

FAP p.Leu212Phe (c.634C>T) is classified Benign in FAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.2575); Low-frequency (popmax 1.21%, afr).

How common is FAP p.Leu212Phe (c.634C>T) in the general population?

FAP p.Leu212Phe (c.634C>T) is low-frequency (popmax 1.21%, afr) (gnomAD).

What do computational predictors say about FAP p.Leu212Phe (c.634C>T)?

AlphaMissense predicts likely benign (score 0.2575) — an in-silico prediction, not a clinical call.

FAP p.Leu212Phe

c.634C>T · rs62001031 · VCV714964

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2575 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2575	likely benign
REVEL	0.485	indeterminate
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.75 · regional, not allelic
Overall
CADD	22.7	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 1.21% African / African-American · 903/74,622 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.0657% 1,056/1,606,372 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.21%	83
Admixed American	0.102%	981
Remaining individualsnot grpmax-eligible	0.101%	986
Middle Eastern	0.0664%	1,507
South Asian	0.00446%	22,408
European (non-Finnish)	0.00187%	53,477

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.Leu212Phe
Coding: c.634C>T
MANE Select: NM_004460
dbSNP: rs62001031
Type: single nucleotide variant
Location: chr2:162218114 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.72 · 4 PDB
Residue 212: 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.Phe185Leu Likely benign ★★ ⚠ same type
FAP p.Ser737= Likely benign ★★ same type
FAP p.Thr229Met Benign ★★ ⚠ same type
FAP p.Tyr458= 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-leu212phe (accessed [today's date]).

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