Is APC p.Ala952Asp (c.2855C>A) pathogenic?

APC p.Ala952Asp (c.2855C>A) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.327); Very rare (popmax 0.0022%, sas); Associated with classic or attenuated familial adenomatous polyposis.

What condition is associated with APC p.Ala952Asp (c.2855C>A)?

APC p.Ala952Asp (c.2855C>A) is associated with classic or attenuated familial adenomatous polyposis, hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Ala952Asp (c.2855C>A) in the general population?

APC p.Ala952Asp (c.2855C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about APC p.Ala952Asp (c.2855C>A)?

AlphaMissense predicts likely benign (score 0.327) — an in-silico prediction, not a clinical call.

APC p.Ala952Asp

c.2855C>A · rs776560257 · VCV236583

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

classic or attenuated familial adenomatous polyposis

Computational evidence

Protein change
AlphaMissense	0.327	likely benign
REVEL	0.45	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.14, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,681 bp · p 0.023 · regional, not allelic
Overall
CADD	17.29	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000867% 14/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
Admixed American	0.00167%	59,982
European (non-Finnish)	0.000932%	107,274

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: APC
Protein: p.Ala952Asp
Coding: c.2855C>A
MANE Select: NM_000038
dbSNP: rs776560257
Type: single nucleotide variant
Location: chr5:112838449 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

classic or attenuated familial adenomatous polyposis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome familial adenomatous polyposis 1

Similar variants

APC p.Ala952Val Uncertain significance ★★ ⚠ same residue
APC p.Ala952= Benign/Likely benign ★★ same residue
APC p.Ala952Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ same condition
APC c.1312+5G>C Likely pathogenic ★★★ same condition
APC c.1409-3T>G Likely pathogenic ★★★ same condition

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/apc-p-ala952asp (accessed [today's date]).

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