Is CD1E p.Arg192Gln (c.575G>A) pathogenic?

CD1E p.Arg192Gln (c.575G>A) is classified Uncertain significance in CD1E (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0973); Very rare (popmax 0.00223%, eas).

How common is CD1E p.Arg192Gln (c.575G>A) in the general population?

CD1E p.Arg192Gln (c.575G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD1E p.Arg192Gln (c.575G>A)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

CD1E p.Arg192Gln

c.575G>A · VCV4222657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.2	GERP -1.1
Regional constraint	o/e 1.04	unconstrained · MANE · 2,904 bp · p 0.34 · regional, not allelic
Overall
CADD	11.98	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000547% 8/1,461,864 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
South Asian	0.0022%	45,535
European (non-Finnish)	0.000424%	236,003

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: CD1E
Protein: p.Arg192Gln
Coding: c.575G>A
MANE Select: NM_030893
Type: single nucleotide variant
Location: chr1:158355519 (GRCh38)
Gene constraint: LOEUF 1.517 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 1 PDB
Residue 192: an α-helix; the ig-like domain

Full CD1E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1E p.Asp264= Benign ★★ same type
CD1E p.His102Arg Benign ★★ same type
CD1E p.Ala110Val Uncertain significance ★ ⚠ same type
CD1E p.Ala127Thr Uncertain significance ★ ⚠ same type
CD1E p.Ala195Val Uncertain significance ★ ⚠ same type
CD1E p.Arg164Trp Uncertain significance ★ ⚠ same type
CD1E p.Arg207Trp Uncertain significance ★ ⚠ same type
CD1E p.Arg270Gln Uncertain significance ★ ⚠ same type

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/cd1e-p-arg192gln (accessed [today's date]).

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