Is CD1A p.Gly240Ser (c.718G>A) pathogenic?

CD1A p.Gly240Ser (c.718G>A) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely benign (0.1756); Ultra-rare (popmax 0.02%, amr).

How common is CD1A p.Gly240Ser (c.718G>A) in the general population?

CD1A p.Gly240Ser (c.718G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about CD1A p.Gly240Ser (c.718G>A)?

AlphaMissense predicts likely benign (score 0.1756) — an in-silico prediction, not a clinical call.

CD1A p.Gly240Ser

c.718G>A · VCV3487876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1756	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -12.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.22	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP -1, phastCons 0.094
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	18.99	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 0.02% Admixed American · 12/60,006 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00384% 62/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.111%	897
Admixed Americangrpmax	0.02%	5,001
Remaining individualsnot grpmax-eligible	0.0112%	8,926
East Asian	0.00223%	44,882
African / African-American	0.00133%	74,940
European (non-Finnish)	0.000678%	147,507

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly240Ser
Coding: c.718G>A
MANE Select: NM_001763
Type: single nucleotide variant
Location: chr1:158256899 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB
Residue 240: a disulfide bond; the ig-like domain

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

Similar variants

CD1A p.Gly240Asp Likely benign ★★ ⚠ same residue
CD1A c.605-3C>T Benign ★★ same type
CD1A p.Arg90Cys 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-gly240ser (accessed [today's date]).

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