Is CLEC18C p.Val28Leu (c.82G>T) pathogenic?

CLEC18C p.Val28Leu (c.82G>T) is classified Uncertain significance in CLEC18C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1097); Ultra-rare (popmax 0.0166%, eas).

How common is CLEC18C p.Val28Leu (c.82G>T) in the general population?

CLEC18C p.Val28Leu (c.82G>T) is ultra-rare (popmax 0.0166%, eas) (gnomAD).

What do computational predictors say about CLEC18C p.Val28Leu (c.82G>T)?

AlphaMissense predicts likely benign (score 0.1097) — an in-silico prediction, not a clinical call.

CLEC18C p.Val28Leu

c.82G>T · rs558004370 · VCV2598205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1097	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -5.69	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 0.32	GERP -2.6, phastCons 0.001
Regional constraint	o/e 0.12	constrained · MANE · 12 kb · p 1e-47 · regional, not allelic
Overall
CADD	2.134	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 0.0166% East Asian · 7/42,092 alleles

Filtering AF 0.00778% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00552%

Overall 0.00118% 17/1,441,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0166%	6,013
Remaining individualsnot grpmax-eligible	0.00703%	14,224
South Asian	0.00229%	43,643
European (non-Finnish)	0.000377%	265,087

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: CLEC18C
Protein: p.Val28Leu
Coding: c.82G>T
MANE Select: NM_173619
dbSNP: rs558004370
Type: single nucleotide variant
Location: chr16:70174360 (GRCh38)
Gene constraint: LOEUF 0.529 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 82.39

Full CLEC18C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC18C p.Ala137Gly Uncertain significance ★ ⚠ same type
CLEC18C p.Ala145Thr Uncertain significance ★ ⚠ same type
CLEC18C p.Ala40Thr Uncertain significance ★ ⚠ same type
CLEC18C p.Ala413Ser Uncertain significance ★ ⚠ same type
CLEC18C p.Ala66Glu Uncertain significance ★ ⚠ same type
CLEC18C p.Ala84Thr Uncertain significance ★ ⚠ same type
CLEC18C p.Arg102Cys Uncertain significance ★ ⚠ same type
CLEC18C p.Arg143Cys 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/clec18c-p-val28leu (accessed [today's date]).

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