Is CLEC4C p.Val71Ile (c.211G>A) pathogenic?

CLEC4C p.Val71Ile (c.211G>A) is classified Uncertain significance in CLEC4C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0806); Very rare (popmax 0.0055%, sas).

How common is CLEC4C p.Val71Ile (c.211G>A) in the general population?

CLEC4C p.Val71Ile (c.211G>A) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about CLEC4C p.Val71Ile (c.211G>A)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

CLEC4C p.Val71Ile

c.211G>A · VCV4654299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.18	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 -6	GERP -2.5
Regional constraint	o/e 0.95	unconstrained · MANE · 18 kb · p 0.41 · regional, not allelic
Overall
CADD	0.532	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 0.0055% South Asian · 5/90,970 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00125% 20/1,606,060 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,194
African / African-American	0.00267%	37,468
East Asian	0.00223%	44,854
Remaining individualsnot grpmax-eligible	0.00161%	62,260
European (non-Finnish)	0.000938%	106,593

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.Val71Ile
Coding: c.211G>A
MANE Select: NM_001371390
Type: single nucleotide variant
Location: chr12:7741445 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 91.84 · 5 PDB
Residue 71: a disulfide bond; a β-strand

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-val71ile (accessed [today's date]).

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