Is APC p.Arg71Cys (c.211C>T) pathogenic?

APC p.Arg71Cys (c.211C>T) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-08). AlphaMissense: ambiguous (0.3424); Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Arg71Cys (c.211C>T)?

APC p.Arg71Cys (c.211C>T) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1, classic or attenuated familial adenomatous polyposis (ClinVar).

How common is APC p.Arg71Cys (c.211C>T) in the general population?

APC p.Arg71Cys (c.211C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about APC p.Arg71Cys (c.211C>T)?

AlphaMissense predicts ambiguous (score 0.3424) — an in-silico prediction, not a clinical call.

APC p.Arg71Cys

c.211C>T · rs767741687 · VCV495354

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.3424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3424	ambiguous
REVEL	0.245	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.82 · regional, not allelic
Overall
CADD	33.0	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 0.00167% Admixed American · 1/59,956 alleles

Filtering AF 0.000692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000541%

Overall 0.000995% 16/1,607,360 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,956
African / African-American	0.00134%	74,714
European (non-Finnish)	0.00119%	83,882

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.Arg71Cys
Coding: c.211C>T
MANE Select: NM_000038
dbSNP: rs767741687
Type: single nucleotide variant
Location: chr5:112766401 (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

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

Also linked: familial adenomatous polyposis 1 classic or attenuated familial adenomatous polyposis

Similar variants

APC p.Arg71Leu Uncertain significance ★★ same residue
APC p.Arg71Pro Uncertain significance ★★ same residue
APC p.Arg71Ser Uncertain significance ★★ ⚠ same residue
APC p.Arg71His Conflicting classifications of pathogenicity ★ ⚠ same residue
APC p.Arg71= Likely benign ★ same residue
APC p.Arg71fs Pathogenic ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G 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-arg71cys (accessed [today's date]).

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