Is CD1C p.Arg283Thr (c.848G>C) pathogenic?

CD1C p.Arg283Thr (c.848G>C) is classified Likely benign in CD1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-13). AlphaMissense: likely benign (0.2459); Rare (popmax 0.553%, afr).

How common is CD1C p.Arg283Thr (c.848G>C) in the general population?

CD1C p.Arg283Thr (c.848G>C) is rare (popmax 0.553%, afr) (gnomAD).

What do computational predictors say about CD1C p.Arg283Thr (c.848G>C)?

AlphaMissense predicts likely benign (score 0.2459) — an in-silico prediction, not a clinical call.

CD1C p.Arg283Thr

c.848G>C · rs139069182 · VCV709334

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2459 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.553%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2459	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.6	GERP -3.1
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	16.17	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 0.553% African / African-American · 415/75,074 alleles

Filtering AF 0.509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.492%

Overall 0.0298% 481/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.553%	181
Admixed American	0.04%	2,501
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0304%	3,290
European (non-Finnish)	0.00178%	56,192

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.Arg283Thr
Coding: c.848G>C
MANE Select: NM_001764 · reported on NM_001765
dbSNP: rs139069182
Type: single nucleotide variant
Location: chr1:158292833 (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-arg283thr (accessed [today's date]).

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