Is CD1C p.Val282Leu (c.844G>T) pathogenic?

CD1C p.Val282Leu (c.844G>T) is classified Likely benign in CD1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). AlphaMissense: ambiguous (0.4976); Rare (popmax 0.306%, nfe).

How common is CD1C p.Val282Leu (c.844G>T) in the general population?

CD1C p.Val282Leu (c.844G>T) is rare (popmax 0.306%, nfe) (gnomAD).

What do computational predictors say about CD1C p.Val282Leu (c.844G>T)?

AlphaMissense predicts ambiguous (score 0.4976) — an in-silico prediction, not a clinical call.

CD1C p.Val282Leu

c.844G>T · rs115248892 · VCV732731

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4976 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.306%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4976	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3	GERP 0.95, phastCons 0.96
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.306% European (non-Finnish) · 3,611/1,180,032 alleles

Filtering AF 0.298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.294%

Overall 0.25% 4,029/1,614,204 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.514%	195
European (non-Finnish)grpmax	0.306%	327
Remaining individualsnot grpmax-eligible	0.218%	460
Admixed American	0.0816%	1,225
Finnishnot grpmax-eligible	0.0781%	1,281
African / African-American	0.0413%	2,422

Ashkenazi Jewish 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: CD1C
Protein: p.Val282Leu
Coding: c.844G>T
MANE Select: NM_001764 · reported on NM_001765
dbSNP: rs115248892
Type: single nucleotide variant
Location: chr1:158292829 (GRCh38)

Full CD1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/cd1c-p-val282leu (accessed [today's date]).

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