Is CD1D p.Trp41Ser (c.122G>C) pathogenic?

CD1D p.Trp41Ser (c.122G>C) is classified Uncertain significance in CD1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.156); Rare (popmax 0.247%, afr).

How common is CD1D p.Trp41Ser (c.122G>C) in the general population?

CD1D p.Trp41Ser (c.122G>C) is rare (popmax 0.247%, afr) (gnomAD).

What do computational predictors say about CD1D p.Trp41Ser (c.122G>C)?

AlphaMissense predicts likely benign (score 0.156) — an in-silico prediction, not a clinical call.

CD1D p.Trp41Ser

c.122G>C · VCV4222654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.156 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.247%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.156	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -11.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP -2.2, phastCons 0.86
Regional constraint	o/e 1.05	unconstrained · MANE · 3,045 bp · p 0.31 · regional, not allelic
Overall
CADD	19.06	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 0.247% African / African-American · 185/75,032 alleles

Filtering AF 0.217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.206%

Overall 0.0122% 197/1,614,156 alleles · rare exomes 87/1,461,872 · genomes 110/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.247%	406
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.00666%	15,006
European (non-Finnish)	8.47e-05%	1,180,026

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.Trp41Ser
Coding: c.122G>C
MANE Select: NM_001371762
Type: single nucleotide variant
Location: chr1:158181515 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.20 · 23 PDB
Residue 41: a β-strand

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-trp41ser (accessed [today's date]).

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