Is CLEC18A p.Ala174Val (c.521C>T) pathogenic?

CLEC18A p.Ala174Val (c.521C>T) is classified Likely benign in CLEC18A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely benign (0.0925); Common (popmax 28.2%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLEC18A p.Ala174Val (c.521C>T)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

CLEC18A p.Ala174Val

Q: How common is CLEC18A p.Ala174Val (c.521C>T) in the general population?

CLEC18A p.Ala174Val (c.521C>T) is common (popmax 28.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.521C>T · rs62053354 · VCV2376870

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 28.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.11	GERP -2.3
Regional constraint	o/e 0.19	constrained · MANE · 9,038 bp · p 8.1e-10 · regional, not allelic
Overall
CADD	7.11	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 28.2% African / African-American · 1,054/3,740 alleles

Filtering AF 26.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.2%

Overall 17.4% 13,236/75,980 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	28.2%	4
Finnishnot grpmax-eligible	25%	4
Amishnot grpmax-eligible	20.2%	5
Ashkenazi Jewishnot grpmax-eligible	19.7%	5
Remaining individualsnot grpmax-eligible	18.7%	5
European (non-Finnish)	17.8%	6
Admixed American	14.3%	7
East Asian	12.6%	8
Middle Eastern	10.2%	10
South Asian	8.6%	12

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: CLEC18A
Protein: p.Ala174Val
Coding: c.521C>T
MANE Select: NM_001370523
dbSNP: rs62053354
Type: single nucleotide variant
Location: chr16:69959006 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 79.11
Residue 174: the scp domain

Full CLEC18A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC18A p.Ala115Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala137Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala142Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala145Thr Uncertain significance ★ ⚠ same type
CLEC18A p.Ala19Ser Uncertain significance ★ ⚠ same type
CLEC18A p.Ala19Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala24Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala37Ser 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/clec18a-p-ala174val (accessed [today's date]).

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