Is CD1B p.Arg264Pro (c.791G>C) pathogenic?

CD1B p.Arg264Pro (c.791G>C) is classified Uncertain significance in CD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely pathogenic (0.6288); Very rare (popmax 8.47e-05%, nfe).

How common is CD1B p.Arg264Pro (c.791G>C) in the general population?

CD1B p.Arg264Pro (c.791G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD1B p.Arg264Pro (c.791G>C)?

AlphaMissense predicts likely pathogenic (score 0.6288) — an in-silico prediction, not a clinical call.

CD1B p.Arg264Pro

c.791G>C · VCV3829421

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6288	likely pathogenic
REVEL	0.247	benign-leaning
SaProt	LLR -10.18	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7	GERP -2.1
Regional constraint	o/e 1.23	unconstrained · MANE · 3,184 bp · p 5.6e-06 · regional, not allelic
Overall
CADD	21.9	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 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.84e-05% 1/1,461,894 alleles · very rare

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.Arg264Pro
Coding: c.791G>C
MANE Select: NM_001764
Type: single nucleotide variant
Location: chr1:158329465 (GRCh38)
Gene constraint: LOEUF 1.334 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 28 PDB
Residue 264: 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.Arg264Gln 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
CD1C p.Val282Leu Likely 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-arg264pro (accessed [today's date]).

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