Is CLEC4F p.Pro545Ala (c.1633C>G) pathogenic?

CLEC4F p.Pro545Ala (c.1633C>G) is classified Uncertain significance in CLEC4F (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0806); Rare (popmax 0.376%, afr).

How common is CLEC4F p.Pro545Ala (c.1633C>G) in the general population?

CLEC4F p.Pro545Ala (c.1633C>G) is rare (popmax 0.376%, afr) (gnomAD).

What do computational predictors say about CLEC4F p.Pro545Ala (c.1633C>G)?

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

CLEC4F p.Pro545Ala

c.1633C>G · VCV4229788

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

rare (popmax 0.376%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -8.50	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 2.9	GERP 1.2, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.038 · regional, not allelic
Overall
CADD	13.34	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 0.376% African / African-American · 282/75,058 alleles

Filtering AF 0.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.326%

Overall 0.0198% 320/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.376%	266
Admixed American	0.0433%	2,308
Remaining individualsnot grpmax-eligible	0.0176%	5,683
European (non-Finnish)	8.48e-05%	1,179,940

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.Pro545Ala
Coding: c.1633C>G
MANE Select: NM_173535
Type: single nucleotide variant
Location: chr2:70809764 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.95
Residue 545: the c-type lectin domain

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.Ala28Gly Uncertain significance ★ ⚠ same type
CLEC4F p.Ala386Gly 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-pro545ala (accessed [today's date]).

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