Is CLEC7A p.Pro95Ser (c.283C>T) pathogenic?

CLEC7A p.Pro95Ser (c.283C>T) is classified Uncertain significance in CLEC7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0929); Very rare (popmax 0.00167%, amr).

How common is CLEC7A p.Pro95Ser (c.283C>T) in the general population?

CLEC7A p.Pro95Ser (c.283C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CLEC7A p.Pro95Ser (c.283C>T)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

CLEC7A p.Pro95Ser

c.283C>T · VCV4837456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.59	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 1.8	GERP -0.34, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.49 · regional, not allelic
Overall
CADD	16.38	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 0.00167% Admixed American · 1/59,748 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,754 alleles · very rare exomes 2/1,460,666 · genomes 1/152,088 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,748
European (non-Finnish)	0.00017%	589,751

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: CLEC7A
Protein: p.Pro95Ser
Coding: c.283C>T
MANE Select: NM_197947
Type: single nucleotide variant
Location: chr12:10126628 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.90

Full CLEC7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC7A p.Pro95Leu Uncertain significance ★ ⚠ same residue
CLEC7A c.*2A>G Benign ★★ same type
CLEC7A p.Ile223Ser Benign ★★ ⚠ same type
CLEC7A p.Leu133= Benign/Likely benign ★★ same type
CLEC7A p.Leu183Phe Benign/Likely benign ★★ ⚠ same type
CLEC7A p.Ser161Leu Benign ★★ same type
CLEC7A p.Tyr238Ter Benign/Likely benign ★★ same type
CLEC7A p.Val63= Likely benign ★★ 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/clec7a-p-pro95ser (accessed [today's date]).

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