Is CD1A p.His55Asp (c.163C>G) pathogenic?

CD1A p.His55Asp (c.163C>G) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: ambiguous (0.5156); Very rare (popmax 0.0011%, sas).

How common is CD1A p.His55Asp (c.163C>G) in the general population?

CD1A p.His55Asp (c.163C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CD1A p.His55Asp (c.163C>G)?

AlphaMissense predicts ambiguous (score 0.5156) — an in-silico prediction, not a clinical call.

CD1A p.His55Asp

c.163C>G · rs1346600075 · VCV2302429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5156 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5156	ambiguous
REVEL	0.076	moderately benign-leaning
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.019	GERP -1.1
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	19.47	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 · 1/91,082 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: CD1A
Protein: p.His55Asp
Coding: c.163C>G
MANE Select: NM_001763
dbSNP: rs1346600075
Type: single nucleotide variant
Location: chr1:158255188 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB
Residue 55: a β-strand

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

Similar variants

CD1A p.His55Leu Uncertain significance ★ ⚠ same residue
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

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-his55asp (accessed [today's date]).

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