Is CD1E p.Leu197Pro (c.590T>C) pathogenic?

CD1E p.Leu197Pro (c.590T>C) is classified Uncertain significance in CD1E (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.8642); Very rare (popmax 0.00833%, amr).

How common is CD1E p.Leu197Pro (c.590T>C) in the general population?

CD1E p.Leu197Pro (c.590T>C) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CD1E p.Leu197Pro (c.590T>C)?

AlphaMissense predicts likely pathogenic (score 0.8642) — an in-silico prediction, not a clinical call.

CD1E p.Leu197Pro

c.590T>C · rs192732251 · VCV2382657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8642	likely pathogenic · top 2% in CD1E
REVEL	0.18	moderately benign-leaning
SaProt	LLR -12.19	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 2.5	GERP 1.9, phastCons 0.098
Regional constraint	o/e 1.04	unconstrained · MANE · 2,904 bp · p 0.34 · regional, not allelic
Overall
CADD	21.1	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 0.00833% Admixed American · 5/60,010 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000805% 13/1,614,080 alleles · very rare exomes 11/1,461,858 · genomes 2/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.000424%	235,998

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.Leu197Pro
Coding: c.590T>C
MANE Select: NM_030893
dbSNP: rs192732251
Type: single nucleotide variant
Location: chr1:158355534 (GRCh38)
Gene constraint: LOEUF 1.517 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 1 PDB
Residue 197: an α-helix; the ig-like domain

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

Similar variants

CD1E p.Leu197Phe Uncertain significance ★ ⚠ same residue
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

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-leu197pro (accessed [today's date]).

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