Is CD1C p.Gln54His (c.162G>T) pathogenic?

CD1C p.Gln54His (c.162G>T) is classified Uncertain significance in CD1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.7226); Ultra-rare (popmax 0.0174%, afr).

How common is CD1C p.Gln54His (c.162G>T) in the general population?

CD1C p.Gln54His (c.162G>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about CD1C p.Gln54His (c.162G>T)?

AlphaMissense predicts likely pathogenic (score 0.7226) — an in-silico prediction, not a clinical call.

CD1C p.Gln54His

c.162G>T · VCV3998046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7226 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7226	likely pathogenic
REVEL	0.048	moderately benign-leaning
SaProt	LLR -10.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.68	GERP -0.017
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	17.59	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 0.0174% African / African-American · 13/74,904 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00118% 19/1,613,958 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,762
Admixed American	0.01%	9,995

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.Gln54His
Coding: c.162G>T
MANE Select: NM_001764 · reported on NM_001765
Type: single nucleotide variant
Location: chr1:158291234 (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-gln54his (accessed [today's date]).

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