Is CLEC3B p.Ala180Asp (c.539C>A) pathogenic?

CLEC3B p.Ala180Asp (c.539C>A) is classified Pathogenic in CLEC3B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely pathogenic (0.5641); Absent from gnomAD v4.1; Associated with macular dystrophy, retinal, 4.

What condition is associated with CLEC3B p.Ala180Asp (c.539C>A)?

CLEC3B p.Ala180Asp (c.539C>A) is associated with macular dystrophy, retinal, 4 (ClinVar).

How common is CLEC3B p.Ala180Asp (c.539C>A) in the general population?

CLEC3B p.Ala180Asp (c.539C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC3B p.Ala180Asp (c.539C>A)?

AlphaMissense predicts likely pathogenic (score 0.5641) — an in-silico prediction, not a clinical call.

CLEC3B p.Ala180Asp

c.539C>A · rs2530665810 · VCV1698394

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5641 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

macular dystrophy, retinal, 4

Computational evidence

Protein change
AlphaMissense	0.5641	likely pathogenic ✓ concordant with ClinVar
REVEL	0.119	moderately benign-leaning
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,558 bp · p 0.11 · regional, not allelic
Overall
CADD	23.5	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

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: CLEC3B
Protein: p.Ala180Asp
Coding: c.539C>A
MANE Select: NM_003278
dbSNP: rs2530665810
Type: single nucleotide variant
Location: chr3:45035854 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 4 PDB
Residue 180: a UniProt-annotated variant site (in mcdr4; leads to thinning in both the outer nuclear layer and whole retina and to impaired retinal function, when tested in a heterologous system); the c-type lectin domain; a turn; a disulfide bond

Full CLEC3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

macular dystrophy, retinal, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLEC3B p.Ala153Ser Uncertain significance ★ ⚠ same type
CLEC3B p.Ala163Val Uncertain significance ★ ⚠ same type
CLEC3B p.Arg151Pro Uncertain significance ★ ⚠ same type
CLEC3B p.Asn114Lys Uncertain significance ★ ⚠ same type
CLEC3B p.Asp166Glu Uncertain significance ★ ⚠ same type
CLEC3B p.Asp191Tyr Uncertain significance ★ ⚠ same type
CLEC3B p.Asp97Gly Uncertain significance ★ ⚠ same type
CLEC3B p.Cys11Tyr 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/clec3b-p-ala180asp (accessed [today's date]).

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