Is CLEC2L p.Ser48Pro (c.142T>C) pathogenic?

CLEC2L p.Ser48Pro (c.142T>C) is classified Uncertain significance in CLEC2L (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.1855); No allele count reported in gnomAD v4.1 (AN 1,225,054).

How common is CLEC2L p.Ser48Pro (c.142T>C) in the general population?

CLEC2L p.Ser48Pro (c.142T>C) is no allele count reported in gnomAD v4.1 (AN 1,225,054) (gnomAD).

What do computational predictors say about CLEC2L p.Ser48Pro (c.142T>C)?

AlphaMissense predicts likely benign (score 0.1855) — an in-silico prediction, not a clinical call.

CLEC2L p.Ser48Pro

c.142T>C · rs2485274950 · VCV2275465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1855 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,225,054)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1855	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.96	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 5.2	GERP 0.03, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 20 kb · p 0.27 · regional, not allelic
Overall
CADD	21.1	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

No allele count reported in gnomAD v4.1 (AN 1,225,054). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLEC2L
Protein: p.Ser48Pro
Coding: c.142T>C
MANE Select: NM_001080511
dbSNP: rs2485274950
Type: single nucleotide variant
Location: chr7:139524069 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.08
Residue 48: 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-ser48pro (accessed [today's date]).

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