Is APCS p.Ile211Thr (c.632T>C) pathogenic?

APCS p.Ile211Thr (c.632T>C) is classified Uncertain significance in APCS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.157); Very rare (popmax 0.00669%, eas).

How common is APCS p.Ile211Thr (c.632T>C) in the general population?

APCS p.Ile211Thr (c.632T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about APCS p.Ile211Thr (c.632T>C)?

AlphaMissense predicts likely benign (score 0.157) — an in-silico prediction, not a clinical call.

APCS p.Ile211Thr

c.632T>C · VCV3413406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.157 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.157	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -4.3
Regional constraint	o/e 1.17	unconstrained · MANE · 783 bp · p 0.0074 · regional, not allelic
Overall
CADD	11.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00669% East Asian · 3/44,856 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000186% 3/1,613,518 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: APCS
Protein: p.Ile211Thr
Coding: c.632T>C
MANE Select: NM_001639
Type: single nucleotide variant
Location: chr1:159588668 (GRCh38)
Gene constraint: LOEUF 1.826 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 94.48 · 13 PDB
Residue 211: the pentraxin (ptx) domain; a β-strand

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

Similar variants

APCS p.Ala146Thr Uncertain significance ★ ⚠ same type
APCS p.Ala58Val Uncertain significance ★ ⚠ same type
APCS p.Arg64His Uncertain significance ★ ⚠ same type
APCS p.Arg86Gly Uncertain significance ★ ⚠ same type
APCS p.Asp203His Uncertain significance ★ ⚠ same type
APCS p.Gln74Glu Uncertain significance ★ ⚠ same type
APCS p.Glu118Lys Uncertain significance ★ ⚠ same type
APCS p.Ile113Asn Uncertain significance ★ ⚠ 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/apcs-p-ile211thr (accessed [today's date]).

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