Is CLEC7A p.Val63= (c.189C>T) pathogenic?

CLEC7A p.Val63= (c.189C>T) is classified Likely benign in CLEC7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-29). Very rare (popmax 0.00249%, nfe).

How common is CLEC7A p.Val63= (c.189C>T) in the general population?

CLEC7A p.Val63= (c.189C>T) is very rare (popmax 0.00249%, nfe) (gnomAD).

CLEC7A p.Val63=

c.189C>T · rs1396267988 · VCV743394

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00249%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor loss, 13 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.97	GERP -0.55, phastCons 1
Overall
CADD	5.626	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00249% European (non-Finnish) · 29/1,165,186 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00151%

Overall 0.00214% 34/1,588,038 alleles · very rare exomes 33/1,436,030 · genomes 1/152,008 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00479%	20,877
Remaining individualsnot grpmax-eligible	0.00324%	30,844
European (non-Finnish)grpmax	0.00249%	40,179

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val63=
Coding: c.189C>T
MANE Select: NM_197947
dbSNP: rs1396267988
Type: single nucleotide variant
Location: chr12:10127760 (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 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.Arg185Gln Uncertain significance ★ ⚠ same type
CLEC7A p.Arg44Cys 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/clec7a-p-val63 (accessed [today's date]).

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