Is CLEC2L p.Ser209Arg (c.625A>C) pathogenic?

CLEC2L p.Ser209Arg (c.625A>C) is classified Uncertain significance in CLEC2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely pathogenic (0.9854); Rare (popmax 0.111%, afr).

How common is CLEC2L p.Ser209Arg (c.625A>C) in the general population?

CLEC2L p.Ser209Arg (c.625A>C) is rare (popmax 0.111%, afr) (gnomAD).

What do computational predictors say about CLEC2L p.Ser209Arg (c.625A>C)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

CLEC2L p.Ser209Arg

c.625A>C · VCV3267683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic
REVEL	0.185	benign-leaning
SaProt	LLR -11.50	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 20 kb · p 0.27 · regional, not allelic
Overall
CADD	27.8	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 0.111% African / African-American · 83/75,030 alleles

Filtering AF 0.0914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0843%

Overall 0.00639% 103/1,612,522 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.111%	904
Admixed American	0.0251%	3,990
Remaining individualsnot grpmax-eligible	0.00641%	15,609
European (non-Finnish)	8.48e-05%	1,179,222

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.Ser209Arg
Coding: c.625A>C
MANE Select: NM_001080511
Type: single nucleotide variant
Location: chr7:139544322 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.08
Residue 209: the c-type lectin domain

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

Similar variants

CLEC2L p.Ser209Ile Uncertain significance ★ ⚠ same residue
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

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-ser209arg (accessed [today's date]).

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