Is CD1A p.Tyr293Cys (c.878A>G) pathogenic?

CD1A p.Tyr293Cys (c.878A>G) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.2228); Very rare (popmax 0.00337%, amr).

How common is CD1A p.Tyr293Cys (c.878A>G) in the general population?

CD1A p.Tyr293Cys (c.878A>G) is very rare (popmax 0.00337%, amr) (gnomAD).

What do computational predictors say about CD1A p.Tyr293Cys (c.878A>G)?

AlphaMissense predicts likely benign (score 0.2228) — an in-silico prediction, not a clinical call.

CD1A p.Tyr293Cys

c.878A>G · VCV4650463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00337%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2228	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -2.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.9
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	22.3	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 0.00337% Admixed American · 2/59,366 alleles

Filtering AF 0.000559% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000187% 3/1,602,864 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00337%	29,683
Remaining individualsnot grpmax-eligible	0.00162%	61,816

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: CD1A
Protein: p.Tyr293Cys
Coding: c.878A>G
MANE Select: NM_001763
Type: single nucleotide variant
Location: chr1:158257059 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB
Residue 293: a β-strand

Full CD1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1A c.605-3C>T Benign ★★ same type
CD1A p.Arg90Cys Benign ★★ ⚠ same type
CD1A p.Gly240Asp Likely benign ★★ ⚠ same type
CD1A p.Ala102Thr Uncertain significance ★ ⚠ same type
CD1A p.Ala196Glu Uncertain significance ★ ⚠ same type
CD1A p.Ala196Ser Uncertain significance ★ ⚠ same type
CD1A p.Ala264Pro Uncertain significance ★ ⚠ same type
CD1A p.Ala306Val 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/cd1a-p-tyr293cys (accessed [today's date]).

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