Is CD1C p.Arg43Gln (c.128G>A) pathogenic?

CD1C p.Arg43Gln (c.128G>A) is classified Likely benign in CD1C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.0709); Ultra-rare (popmax 0.0164%, mid).

How common is CD1C p.Arg43Gln (c.128G>A) in the general population?

CD1C p.Arg43Gln (c.128G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CD1C p.Arg43Gln (c.128G>A)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

CD1C p.Arg43Gln

c.128G>A · VCV3487896

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP -3.7
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	1.812	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00266% 43/1,613,572 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	0.00305%	32,776
East Asian	0.00223%	44,862
South Asian	0.0022%	45,530

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.Arg43Gln
Coding: c.128G>A
MANE Select: NM_001764 · reported on NM_001765
Type: single nucleotide variant
Location: chr1:158291200 (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-arg43gln (accessed [today's date]).

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