Is CD302 p.Pro12Ser (c.34C>T) pathogenic?

CD302 p.Pro12Ser (c.34C>T) is classified Uncertain significance in CD302 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.1404); Ultra-rare (popmax 0.0116%, amr).

How common is CD302 p.Pro12Ser (c.34C>T) in the general population?

CD302 p.Pro12Ser (c.34C>T) is ultra-rare (popmax 0.0116%, amr) (gnomAD).

What do computational predictors say about CD302 p.Pro12Ser (c.34C>T)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

CD302 p.Pro12Ser

c.34C>T · VCV3488047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.69	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 3.8	GERP 0.66, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 26 kb · p 0.38 · regional, not allelic
Overall
CADD	17.42	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 0.0116% Admixed American · 5/43,060 alleles

Filtering AF 0.00449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00054% 8/1,482,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0116%	8,612
African / African-American	0.00293%	34,173
Remaining individualsnot grpmax-eligible	0.00174%	57,362

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: CD302
Protein: p.Pro12Ser
Coding: c.34C>T
MANE Select: NM_014880
Type: single nucleotide variant
Location: chr2:159798165 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.53 · 1 PDB

Full CD302 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD302 p.Ala5Thr Uncertain significance ★ ⚠ same type
CD302 p.Asp113Gly Uncertain significance ★ ⚠ same type
CD302 p.Leu6Arg Uncertain significance ★ ⚠ same type
CD302 p.Leu9Arg Uncertain significance ★ ⚠ same type
CD302 p.Pro7Arg Uncertain significance ★ ⚠ same type
LY75-CD302 p.Ser1840Pro 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/cd302-p-pro12ser (accessed [today's date]).

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