Is CD1B p.Arg240Gln (c.719G>A) pathogenic?

CD1B p.Arg240Gln (c.719G>A) is classified Likely benign in CD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.0835); Very rare (popmax 0.00329%, sas).

How common is CD1B p.Arg240Gln (c.719G>A) in the general population?

CD1B p.Arg240Gln (c.719G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CD1B p.Arg240Gln (c.719G>A)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

CD1B p.Arg240Gln

c.719G>A · rs763828715 · VCV2472670

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.8	GERP -3
Regional constraint	o/e 1.23	unconstrained · MANE · 3,184 bp · p 5.6e-06 · regional, not allelic
Overall
CADD	16.33	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00124% 20/1,613,910 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Admixed American	0.00167%	59,992
European (non-Finnish)	0.00136%	73,750

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.Arg240Gln
Coding: c.719G>A
MANE Select: NM_001764
dbSNP: rs763828715
Type: single nucleotide variant
Location: chr1:158329537 (GRCh38)
Gene constraint: LOEUF 1.334 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 28 PDB
Residue 240: a disulfide bond; a β-strand; the ig-like domain

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

Similar variants

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
CD1C p.Val282Leu Likely benign ★★ ⚠ same type
CD1C p.Val318= 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-arg240gln (accessed [today's date]).

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