Is CLEC4F p.Val369Ala (c.1106T>C) pathogenic?

CLEC4F p.Val369Ala (c.1106T>C) is classified Benign in CLEC4F (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-27). AlphaMissense: likely benign (0.0664); Common (popmax 5.56%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLEC4F p.Val369Ala (c.1106T>C)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

CLEC4F p.Val369Ala

Q: How common is CLEC4F p.Val369Ala (c.1106T>C) in the general population?

CLEC4F p.Val369Ala (c.1106T>C) is common (popmax 5.56%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1106T>C · rs34318515 · VCV775726

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.56%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -5.76	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 0.29	GERP -1.9
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.038 · regional, not allelic
Overall
CADD	1.167	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 5.56% African / African-American · 4,170/75,058 alleles

Filtering AF 5.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.36%

Overall 0.291% 4,695/1,614,222 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.56%	18
Middle Eastern	0.412%	242
Remaining individualsnot grpmax-eligible	0.386%	259
Admixed American	0.338%	296
South Asian	0.00769%	13,012
European (non-Finnish)	0.00415%	24,082

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.Val369Ala
Coding: c.1106T>C
MANE Select: NM_173535
dbSNP: rs34318515
Type: single nucleotide variant
Location: chr2:70816275 (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.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
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-val369ala (accessed [today's date]).

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