Is CLEC4F p.Phe200Ile (c.598T>A) pathogenic?

CLEC4F p.Phe200Ile (c.598T>A) is classified Uncertain significance in CLEC4F (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.03%, amr).

How common is CLEC4F p.Phe200Ile (c.598T>A) in the general population?

CLEC4F p.Phe200Ile (c.598T>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about CLEC4F p.Phe200Ile (c.598T>A)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

CLEC4F p.Phe200Ile

c.598T>A · rs782576049 · VCV3145702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.17	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 1	GERP -2.5, phastCons 0.04
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.038 · regional, not allelic
Overall
CADD	10.46	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 0.03% Admixed American · 18/60,010 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00112% 18/1,613,972 alleles · ultra-rare

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.Phe200Ile
Coding: c.598T>A
MANE Select: NM_173535
dbSNP: rs782576049
Type: single nucleotide variant
Location: chr2:70816783 (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.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-phe200ile (accessed [today's date]).

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