Is CD1C p.Arg213Cys (c.637C>T) pathogenic?

CD1C p.Arg213Cys (c.637C>T) is classified Uncertain significance in CD1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.1704); Very rare (popmax 0.00659%, sas).

How common is CD1C p.Arg213Cys (c.637C>T) in the general population?

CD1C p.Arg213Cys (c.637C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CD1C p.Arg213Cys (c.637C>T)?

AlphaMissense predicts likely benign (score 0.1704) — an in-silico prediction, not a clinical call.

CD1C p.Arg213Cys

c.637C>T · VCV3998047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1704	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -10.70	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	14.46	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 0.00659% South Asian · 6/91,002 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00136% 22/1,612,762 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,167
East Asian	0.00223%	44,904
African / African-American	0.00134%	74,898
European (non-Finnish)	0.00119%	84,285

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.Arg213Cys
Coding: c.637C>T
MANE Select: NM_001764 · reported on NM_001765
Type: single nucleotide variant
Location: chr1:158292622 (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-arg213cys (accessed [today's date]).

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