Is CD1B p.Gln330Glu (c.988C>G) pathogenic?

CD1B p.Gln330Glu (c.988C>G) is classified Uncertain significance in CD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0715); Very rare (popmax 0.00968%, nfe).

How common is CD1B p.Gln330Glu (c.988C>G) in the general population?

CD1B p.Gln330Glu (c.988C>G) is very rare (popmax 0.00968%, nfe) (gnomAD).

What do computational predictors say about CD1B p.Gln330Glu (c.988C>G)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

CD1B p.Gln330Glu

c.988C>G · rs370087365 · VCV3140385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00968%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.23 · evaluated, not missing
Pangolin	Δ0.22	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.74	GERP -1.8, phastCons 0.52
Regional constraint	o/e 1.23	unconstrained · MANE · 3,184 bp · p 5.6e-06 · regional, not allelic
Overall
CADD	10.47	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 0.00968% European (non-Finnish) · 114/1,178,140 alleles

Filtering AF 0.00819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00762%

Overall 0.0072% 116/1,611,572 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00968%	10,335
Remaining individualsnot grpmax-eligible	0.00321%	31,187

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: CD1B
Protein: p.Gln330Glu
Coding: c.988C>G
MANE Select: NM_001764
dbSNP: rs370087365
Type: single nucleotide variant
Location: chr1:158328250 (GRCh38)
Gene constraint: LOEUF 1.334 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 28 PDB

Full CD1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1B p.Gln330Arg Uncertain significance ★ ⚠ same residue
CD1C p.Gln330Leu Uncertain significance ★ ⚠ same residue
CD1B p.Gly104Ser Benign ★★ same type
CD1B p.Gly247Ser Benign ★★ ⚠ same type
CD1B p.Phe76= Benign ★★ same type
CD1C p.Arg283Thr Likely benign ★★ ⚠ same type
CD1C p.Gln23= Benign ★★ same type
CD1C p.Phe300Ser Benign ★★ 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/cd1b-p-gln330glu (accessed [today's date]).

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