Is APCS p.His97= (c.291C>T) pathogenic?

APCS p.His97= (c.291C>T) is classified Likely benign in APCS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-01). Absent from gnomAD v4.1.

How common is APCS p.His97= (c.291C>T) in the general population?

APCS p.His97= (c.291C>T) is absent from gnomAD v4.1 (gnomAD).

APCS p.His97=

c.291C>T · VCV3390076

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -4.2
Overall
CADD	0.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APCS
Protein: p.His97=
Coding: c.291C>T
MANE Select: NM_001639
Type: single nucleotide variant
Location: chr1:159588327 (GRCh38)
Gene constraint: LOEUF 1.826 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 94.48 · 13 PDB
Residue 97: a disulfide bond; a β-strand; the pentraxin (ptx) domain

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-his97 (accessed [today's date]).

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