Is CD1B p.Tyr262Cys (c.785A>G) pathogenic?

CD1B p.Tyr262Cys (c.785A>G) is classified Uncertain significance in CD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.6039); Very rare (popmax 0.0011%, sas).

How common is CD1B p.Tyr262Cys (c.785A>G) in the general population?

CD1B p.Tyr262Cys (c.785A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CD1B p.Tyr262Cys (c.785A>G)?

AlphaMissense predicts likely pathogenic (score 0.6039) — an in-silico prediction, not a clinical call.

CD1B p.Tyr262Cys

c.785A>G · rs2525812789 · VCV3140380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6039 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6039	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP 0.62, phastCons 0.95
Regional constraint	o/e 1.23	unconstrained · MANE · 3,184 bp · p 5.6e-06 · regional, not allelic
Overall
CADD	24.9	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 0.0011% South Asian · 1/91,084 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	0.000254%	393,345

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.Tyr262Cys
Coding: c.785A>G
MANE Select: NM_001764
dbSNP: rs2525812789
Type: single nucleotide variant
Location: chr1:158329471 (GRCh38)
Gene constraint: LOEUF 1.334 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 28 PDB
Residue 262: 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-tyr262cys (accessed [today's date]).

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