Is APC p.Ala160Ser (c.478G>T) pathogenic?

APC p.Ala160Ser (c.478G>T) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-26). AlphaMissense: likely benign (0.0764); Very rare (popmax 0.00224%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Ala160Ser (c.478G>T)?

APC p.Ala160Ser (c.478G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is APC p.Ala160Ser (c.478G>T) in the general population?

APC p.Ala160Ser (c.478G>T) is very rare (popmax 0.00224%, sas) (gnomAD).

What do computational predictors say about APC p.Ala160Ser (c.478G>T)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

APC p.Ala160Ser

c.478G>T · rs1114167556 · VCV1172191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.387	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.82 · regional, not allelic
Overall
CADD	24.9	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 0.00224% South Asian · 2/89,164 alleles

Filtering AF 0.000372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000139%

Overall 0.000124% 2/1,607,212 alleles · very rare exomes 2/1,455,526 · genomes 0/151,686 · joint denominator

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.Ala160Ser
Coding: c.478G>T
MANE Select: NM_000038
dbSNP: rs1114167556
Type: single nucleotide variant
Location: chr5:112775684 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 160: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APC p.Ala160Thr Uncertain significance ★★ same residue
APC p.Ala160= Benign/Likely benign ★★ same residue
APC p.Ala160Val Uncertain significance ★ same residue
APC p.Ala160Pro Uncertain significance ★ 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

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-ala160ser (accessed [today's date]).

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