Is HPCA p.Ala53= (c.159C>T) pathogenic?

HPCA p.Ala53= (c.159C>T) is classified Likely benign in HPCA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Absent from gnomAD v4.1.

How common is HPCA p.Ala53= (c.159C>T) in the general population?

HPCA p.Ala53= (c.159C>T) is absent from gnomAD v4.1 (gnomAD).

HPCA p.Ala53=

c.159C>T · rs2522530553 · VCV2864321

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 6	GERP 2.6, phastCons 1
Overall
CADD	16.06	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: HPCA
Protein: p.Ala53=
Coding: c.159C>T
MANE Select: NM_002143
dbSNP: rs2522530553
Type: single nucleotide variant
Location: chr1:32889057 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.87 · 4 PDB
Residue 53: the ef-hand 1 domain; an α-helix

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

Similar variants

HPCA p.Lys147Met Uncertain significance ★★ same type
HPCA c.484+32G>C Likely benign ★★ same type
HPCA c.379-3C>T Uncertain significance ★ same type
HPCA c.-5C>T Uncertain significance ★ same type
HPCA p.Ala127Thr Uncertain significance ★ ⚠ same type
HPCA p.Ala88Glu Uncertain significance ★ ⚠ same type
HPCA p.Arg118Gln Uncertain significance ★ ⚠ same type
HPCA p.Arg17Gln 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/hpca-p-ala53 (accessed [today's date]).

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