Is CLEC4A p.Ala102Pro (c.304G>C) pathogenic?

CLEC4A p.Ala102Pro (c.304G>C) is classified Uncertain significance in CLEC4A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.1172); Very rare (popmax 0.00534%, afr).

How common is CLEC4A p.Ala102Pro (c.304G>C) in the general population?

CLEC4A p.Ala102Pro (c.304G>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CLEC4A p.Ala102Pro (c.304G>C)?

AlphaMissense predicts likely benign (score 0.1172) — an in-silico prediction, not a clinical call.

CLEC4A p.Ala102Pro

c.304G>C · VCV4003561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1172 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1172	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -7.99	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 -0.97	GERP -2.4
Regional constraint	o/e 0.92	unconstrained · MANE · 14 kb · p 0.19 · regional, not allelic
Overall
CADD	16.87	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 0.00534% African / African-American · 4/74,942 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00217% 35/1,613,996 alleles · very rare exomes 27/1,461,768 · genomes 8/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,736
European (non-Finnish)	0.00246%	40,689
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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: CLEC4A
Protein: p.Ala102Pro
Coding: c.304G>C
MANE Select: NM_016184
Type: single nucleotide variant
Location: chr12:8135590 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.95 · 2 PDB

Full CLEC4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4A p.Arg194Cys Uncertain significance ★★ ⚠ same type
CLEC4A p.Ter238Arg Benign ★★ same type
CLEC4A p.Arg174Gln Uncertain significance ★ ⚠ same type
CLEC4A p.Arg202Cys Uncertain significance ★ ⚠ same type
CLEC4A p.Arg202His Uncertain significance ★ ⚠ same type
CLEC4A p.Arg209Cys Uncertain significance ★ ⚠ same type
CLEC4A p.Arg209His Uncertain significance ★ ⚠ same type
CLEC4A p.Asn185Asp 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/clec4a-p-ala102pro (accessed [today's date]).

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