Is CD1A p.Ala264Pro (c.790G>C) pathogenic?

CD1A p.Ala264Pro (c.790G>C) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.7748); Very rare (popmax 0.00932%, nfe).

How common is CD1A p.Ala264Pro (c.790G>C) in the general population?

CD1A p.Ala264Pro (c.790G>C) is very rare (popmax 0.00932%, nfe) (gnomAD).

What do computational predictors say about CD1A p.Ala264Pro (c.790G>C)?

AlphaMissense predicts likely pathogenic (score 0.7748) — an in-silico prediction, not a clinical call.

CD1A p.Ala264Pro

c.790G>C · VCV4222628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7748	likely pathogenic · top 3% in CD1A
REVEL	0.166	moderately benign-leaning
SaProt	LLR -14.33	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP 0.92
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	17.43	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 0.00932% European (non-Finnish) · 110/1,180,042 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00719% 116/1,614,058 alleles · very rare exomes 105/1,461,890 · genomes 11/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00932%	10,728
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00167%	60,004
African / African-American	0.00133%	74,930

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.Ala264Pro
Coding: c.790G>C
MANE Select: NM_001763
Type: single nucleotide variant
Location: chr1:158256971 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB
Residue 264: a β-strand; the ig-like domain

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.Ala306Val Uncertain significance ★ ⚠ same type
CD1A p.Arg185Cys 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-ala264pro (accessed [today's date]).

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