Is CLEC12A p.Pro33Ala (c.97C>G) pathogenic?

CLEC12A p.Pro33Ala (c.97C>G) is classified Uncertain significance in CLEC12A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.0588); Absent from gnomAD v4.1.

How common is CLEC12A p.Pro33Ala (c.97C>G) in the general population?

CLEC12A p.Pro33Ala (c.97C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC12A p.Pro33Ala (c.97C>G)?

AlphaMissense predicts likely benign (score 0.0588) — an in-silico prediction, not a clinical call.

CLEC12A p.Pro33Ala

c.97C>G · rs1289581250 · VCV3145554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0588 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0588	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.73	GERP -0.99
Regional constraint	o/e 1.12	unconstrained · MANE · 13 kb · p 0.036 · regional, not allelic
Overall
CADD	0.356	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

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: CLEC12A
Protein: p.Pro33Ala
Coding: c.97C>G
MANE Select: NM_138337
dbSNP: rs1289581250
Type: single nucleotide variant
Location: chr12:9978971 (GRCh38)
Gene constraint: LOEUF 1.366 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.35 · 3 PDB

Full CLEC12A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC12A c.-3T>C Uncertain significance ★ same type
CLEC12A p.Ala163Thr Uncertain significance ★ ⚠ same type
CLEC12A p.Ala166Asp Uncertain significance ★ ⚠ same type
CLEC12A p.Ala166Val Uncertain significance ★ ⚠ same type
CLEC12A p.Ala176Ser Uncertain significance ★ ⚠ same type
CLEC12A p.Arg119Cys Uncertain significance ★ ⚠ same type
CLEC12A p.Asn101Ser Uncertain significance ★ ⚠ same type
CLEC12A p.Asn105Lys 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/clec12a-p-pro33ala (accessed [today's date]).

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