Is CD1D p.Leu191Phe (c.571C>T) pathogenic?

CD1D p.Leu191Phe (c.571C>T) is classified Uncertain significance in CD1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.2476); Very rare (popmax 0.0011%, sas).

How common is CD1D p.Leu191Phe (c.571C>T) in the general population?

CD1D p.Leu191Phe (c.571C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CD1D p.Leu191Phe (c.571C>T)?

AlphaMissense predicts likely benign (score 0.2476) — an in-silico prediction, not a clinical call.

CD1D p.Leu191Phe

c.571C>T · rs768667642 · VCV2601846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2476 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2476	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -1.9
Regional constraint	o/e 1.05	unconstrained · MANE · 3,045 bp · p 0.31 · regional, not allelic
Overall
CADD	15.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.000847%	118,003

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: CD1D
Protein: p.Leu191Phe
Coding: c.571C>T
MANE Select: NM_001371762
dbSNP: rs768667642
Type: single nucleotide variant
Location: chr1:158182274 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.20 · 23 PDB
Residue 191: an α-helix; the ig-like domain

Full CD1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1D p.Thr64Ser Benign ★★ same type
CD1D p.Ala118Ser Uncertain significance ★ ⚠ same type
CD1D p.Ala11Glu Uncertain significance ★ ⚠ same type
CD1D p.Ala306Ser Uncertain significance ★ ⚠ same type
CD1D p.Ala311Val Uncertain significance ★ ⚠ same type
CD1D p.Arg211His Uncertain significance ★ ⚠ same type
CD1D p.Arg24Lys Uncertain significance ★ ⚠ same type
CD1D p.Arg280Gly 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/cd1d-p-leu191phe (accessed [today's date]).

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