Is CLEC4A p.Pro43Ser (c.127C>T) pathogenic?

CLEC4A p.Pro43Ser (c.127C>T) is classified Likely benign in CLEC4A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0942); Ultra-rare (popmax 0.0134%, eas).

How common is CLEC4A p.Pro43Ser (c.127C>T) in the general population?

CLEC4A p.Pro43Ser (c.127C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CLEC4A p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

CLEC4A p.Pro43Ser

c.127C>T · VCV4229764

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -3.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.5	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 14 kb · p 0.19 · regional, not allelic
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,860 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000496% 8/1,613,408 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,477
Admixed American	0.00167%	59,982
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Pro43Ser
Coding: c.127C>T
MANE Select: NM_016184
Type: single nucleotide variant
Location: chr12:8125605 (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.Ala102Pro Uncertain significance ★ ⚠ 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

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-pro43ser (accessed [today's date]).

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