Is CLEC5A p.Ser53Arg (c.159C>A) pathogenic?

CLEC5A p.Ser53Arg (c.159C>A) is classified Uncertain significance in CLEC5A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely benign (0.1385); Very rare (popmax 8.5e-05%, nfe).

How common is CLEC5A p.Ser53Arg (c.159C>A) in the general population?

CLEC5A p.Ser53Arg (c.159C>A) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about CLEC5A p.Ser53Arg (c.159C>A)?

AlphaMissense predicts likely benign (score 0.1385) — an in-silico prediction, not a clinical call.

CLEC5A p.Ser53Arg

c.159C>A · rs2485546302 · VCV2276240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1385 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1385	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.4	GERP 0.96
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.39 · regional, not allelic
Overall
CADD	3.327	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 8.5e-05% European (non-Finnish) · 1/1,176,112 alleles

Overall 6.21e-05% 1/1,609,448 alleles · very rare exomes 1/1,457,252 · genomes 0/152,196 · joint denominator

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: CLEC5A
Protein: p.Ser53Arg
Coding: c.159C>A
MANE Select: NM_013252
dbSNP: rs2485546302
Type: single nucleotide variant
Location: chr7:141943945 (GRCh38)
Gene constraint: LOEUF 1.613 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.83 · 1 PDB

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-ser53arg (accessed [today's date]).

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