Is CLEC4F p.Ala28Gly (c.83C>G) pathogenic?

CLEC4F p.Ala28Gly (c.83C>G) is classified Uncertain significance in CLEC4F (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.0964); Ultra-rare (popmax 0.0215%, afr).

How common is CLEC4F p.Ala28Gly (c.83C>G) in the general population?

CLEC4F p.Ala28Gly (c.83C>G) is ultra-rare (popmax 0.0215%, afr) (gnomAD).

What do computational predictors say about CLEC4F p.Ala28Gly (c.83C>G)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

CLEC4F p.Ala28Gly

c.83C>G · VCV3493585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0215%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP 0.21, phastCons 0.38
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.038 · regional, not allelic
Overall
CADD	6.181	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 0.0215% African / African-American · 16/74,422 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.00106% 17/1,600,374 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0215%	4,651
European (non-Finnish)	8.52e-05%	1,174,115

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: CLEC4F
Protein: p.Ala28Gly
Coding: c.83C>G
MANE Select: NM_173535
Type: single nucleotide variant
Location: chr2:70819870 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95

Full CLEC4F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC4F p.Asn146Ser Benign ★★ same type
CLEC4F p.Thr235Met Benign/Likely benign ★★ ⚠ same type
CLEC4F p.Val369Ala Benign ★★ same type
CLEC4F p.Ala192Thr Uncertain significance ★ ⚠ same type
CLEC4F p.Ala222Thr Uncertain significance ★ ⚠ same type
CLEC4F p.Ala26Thr Uncertain significance ★ ⚠ same type
CLEC4F p.Ala386Gly Uncertain significance ★ ⚠ same type
CLEC4F p.Ala402Gly 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/clec4f-p-ala28gly (accessed [today's date]).

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