Is FAP p.Asp108Val (c.323A>T) pathogenic?

FAP p.Asp108Val (c.323A>T) is classified Uncertain significance in FAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: likely pathogenic (0.8335); Very rare (popmax 0.00451%, eas).

How common is FAP p.Asp108Val (c.323A>T) in the general population?

FAP p.Asp108Val (c.323A>T) is very rare (popmax 0.00451%, eas) (gnomAD).

What do computational predictors say about FAP p.Asp108Val (c.323A>T)?

AlphaMissense predicts likely pathogenic (score 0.8335) — an in-silico prediction, not a clinical call.

FAP p.Asp108Val

c.323A>T · VCV4022909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8335 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00451%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8335	likely pathogenic
REVEL	0.851	moderately pathogenic-leaning
SaProt	LLR -14.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.28	acceptor loss, 37 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.75 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00451% East Asian · 2/44,308 alleles

Filtering AF 0.000748% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00028%

Overall 0.000138% 2/1,449,478 alleles · very rare

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.Asp108Val
Coding: c.323A>T
MANE Select: NM_004460
Type: single nucleotide variant
Location: chr2:162224503 (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-asp108val (accessed [today's date]).

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