Is CLEC5A p.Asp97Glu (c.291C>A) pathogenic?

CLEC5A p.Asp97Glu (c.291C>A) is classified Uncertain significance in CLEC5A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.1456); Absent from gnomAD v4.1.

How common is CLEC5A p.Asp97Glu (c.291C>A) in the general population?

CLEC5A p.Asp97Glu (c.291C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC5A p.Asp97Glu (c.291C>A)?

AlphaMissense predicts likely benign (score 0.1456) — an in-silico prediction, not a clinical call.

CLEC5A p.Asp97Glu

c.291C>A · VCV4654328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1456 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1456	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -6.79	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 0.019	GERP -2.3
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.39 · regional, not allelic
Overall
CADD	1.14	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

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: CLEC5A
Protein: p.Asp97Glu
Coding: c.291C>A
MANE Select: NM_013252
Type: single nucleotide variant
Location: chr7:141935868 (GRCh38)
Gene constraint: LOEUF 1.613 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.83 · 1 PDB
Residue 97: an α-helix; the c-type lectin domain

Full CLEC5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC5A p.Ala162Gly Uncertain significance ★ ⚠ same type
CLEC5A p.Arg135Cys Uncertain significance ★ ⚠ same type
CLEC5A p.Arg135His Uncertain significance ★ ⚠ same type
CLEC5A p.Arg141Cys Uncertain significance ★ ⚠ same type
CLEC5A p.Arg180Cys Uncertain significance ★ ⚠ same type
CLEC5A p.Arg180His Uncertain significance ★ ⚠ same type
CLEC5A p.Arg180Leu Uncertain significance ★ ⚠ same type
CLEC5A p.Asn32Ser 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/clec5a-p-asp97glu (accessed [today's date]).

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