Is CD1E p.Val240Met (c.718G>A) pathogenic?

CD1E p.Val240Met (c.718G>A) is classified Uncertain significance in CD1E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.2309); Ultra-rare (popmax 0.0165%, mid).

How common is CD1E p.Val240Met (c.718G>A) in the general population?

CD1E p.Val240Met (c.718G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD1E p.Val240Met (c.718G>A)?

AlphaMissense predicts likely benign (score 0.2309) — an in-silico prediction, not a clinical call.

CD1E p.Val240Met

c.718G>A · VCV3264759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2309 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2309	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -12.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -2.4
Regional constraint	o/e 1.04	unconstrained · MANE · 2,904 bp · p 0.34 · regional, not allelic
Overall
CADD	19.37	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 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00229% 37/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
South Asian	0.00878%	11,385
East Asian	0.00446%	22,425
Admixed American	0.00333%	30,013
European (non-Finnish)	0.00195%	51,305
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: CD1E
Protein: p.Val240Met
Coding: c.718G>A
MANE Select: NM_030893
Type: single nucleotide variant
Location: chr1:158355919 (GRCh38)
Gene constraint: LOEUF 1.517 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 1 PDB
Residue 240: a β-strand; the ig-like domain; a disulfide bond

Full CD1E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1E p.Asp264= Benign ★★ same type
CD1E p.His102Arg Benign ★★ same type
CD1E p.Ala110Val Uncertain significance ★ ⚠ same type
CD1E p.Ala127Thr Uncertain significance ★ ⚠ same type
CD1E p.Ala195Val Uncertain significance ★ ⚠ same type
CD1E p.Arg164Trp Uncertain significance ★ ⚠ same type
CD1E p.Arg192Gln Uncertain significance ★ ⚠ same type
CD1E p.Arg207Trp 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/cd1e-p-val240met (accessed [today's date]).

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