Is CLEC14A p.Trp130Cys (c.390G>C) pathogenic?

CLEC14A p.Trp130Cys (c.390G>C) is classified Uncertain significance in CLEC14A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely pathogenic (0.9989); Absent from gnomAD v4.1.

How common is CLEC14A p.Trp130Cys (c.390G>C) in the general population?

CLEC14A p.Trp130Cys (c.390G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC14A p.Trp130Cys (c.390G>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

CLEC14A p.Trp130Cys

c.390G>C · VCV3493505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 1% in CLEC14A
REVEL	0.425	indeterminate
SaProt	LLR -14.01	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,469 bp · p 0.39 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLEC14A
Protein: p.Trp130Cys
Coding: c.390G>C
MANE Select: NM_175060
Type: single nucleotide variant
Location: chr14:38255633 (GRCh38)
Gene constraint: LOEUF 1.883 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 69.00
Residue 130: the c-type lectin domain

Full CLEC14A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC14A p.Ser395= Benign ★★ same type
CLEC14A p.Ala140Ser Uncertain significance ★ ⚠ same type
CLEC14A p.Ala155Ser Uncertain significance ★ ⚠ same type
CLEC14A p.Ala186Val Uncertain significance ★ ⚠ same type
CLEC14A p.Ala228Gly Uncertain significance ★ ⚠ same type
CLEC14A p.Ala233Val Uncertain significance ★ ⚠ same type
CLEC14A p.Ala257Ser Uncertain significance ★ ⚠ same type
CLEC14A p.Ala308Pro 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/clec14a-p-trp130cys (accessed [today's date]).

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