Is CLEC4C p.Val34Asp (c.101T>A) pathogenic?

CLEC4C p.Val34Asp (c.101T>A) is classified Uncertain significance in CLEC4C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-12). AlphaMissense: ambiguous (0.522); Very rare (popmax 0.00833%, amr).

How common is CLEC4C p.Val34Asp (c.101T>A) in the general population?

CLEC4C p.Val34Asp (c.101T>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CLEC4C p.Val34Asp (c.101T>A)?

AlphaMissense predicts ambiguous (score 0.522) — an in-silico prediction, not a clinical call.

CLEC4C p.Val34Asp

c.101T>A · VCV4229771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.522 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.522	ambiguous
REVEL	0.063	moderately benign-leaning
SaProt	LLR -12.70	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3.2
Regional constraint	o/e 0.95	unconstrained · MANE · 18 kb · p 0.41 · regional, not allelic
Overall
CADD	12.63	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 0.00833% Admixed American · 5/59,994 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,613,288 alleles · very rare exomes 5/1,461,014 · genomes 0/152,274 · joint denominator

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: CLEC4C
Protein: p.Val34Asp
Coding: c.101T>A
MANE Select: NM_001371390
Type: single nucleotide variant
Location: chr12:7746354 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 91.84 · 5 PDB

Full CLEC4C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4C p.Asn122Lys Benign ★★ same type
CLEC4C p.Leu58Val Benign ★★ same type
CLEC4C p.Ala116Ser Uncertain significance ★ ⚠ same type
CLEC4C p.Ala181Thr Uncertain significance ★ ⚠ same type
CLEC4C p.Arg150Gln Uncertain significance ★ ⚠ same type
CLEC4C p.Arg186Cys Uncertain significance ★ ⚠ same type
CLEC4C p.Arg186His Uncertain significance ★ ⚠ same type
CLEC4C p.Asn162Asp 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/clec4c-p-val34asp (accessed [today's date]).

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