Is CLEC2L p.Pro14Ser (c.40C>T) pathogenic?

CLEC2L p.Pro14Ser (c.40C>T) is classified Uncertain significance in CLEC2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely benign (0.091); Rare (popmax 0.197%, nfe).

How common is CLEC2L p.Pro14Ser (c.40C>T) in the general population?

CLEC2L p.Pro14Ser (c.40C>T) is rare (popmax 0.197%, nfe) (gnomAD).

What do computational predictors say about CLEC2L p.Pro14Ser (c.40C>T)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

CLEC2L p.Pro14Ser

c.40C>T · rs939400523 · VCV2346370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.197%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -9.18	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 2.9	GERP 0.65, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 20 kb · p 0.27 · regional, not allelic
Overall
CADD	17.43	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 0.197% European (non-Finnish) · 1,618/819,380 alleles

Filtering AF 0.189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.176% 1,707/970,856 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.197%	506
Remaining individualsnot grpmax-eligible	0.169%	592
Admixed American	0.0635%	1,574
Middle Eastern	0.0526%	1,900
South Asian	0.0508%	1,969
African / African-American	0.0319%	3,137

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: CLEC2L
Protein: p.Pro14Ser
Coding: c.40C>T
MANE Select: NM_001080511
dbSNP: rs939400523
Type: single nucleotide variant
Location: chr7:139523967 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.08
Residue 14: the 'disordered' region

Full CLEC2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC2L c.432+1G>T Uncertain significance ★ same type
CLEC2L p.Ala182Thr Uncertain significance ★ ⚠ same type
CLEC2L p.Ala24Val Uncertain significance ★ ⚠ same type
CLEC2L p.Ala26Gly Uncertain significance ★ ⚠ same type
CLEC2L p.Ala27Thr Uncertain significance ★ ⚠ same type
CLEC2L p.Ala34Ser Uncertain significance ★ ⚠ same type
CLEC2L p.Ala34Thr Uncertain significance ★ ⚠ same type
CLEC2L p.Ala80Thr 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/clec2l-p-pro14ser (accessed [today's date]).

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