Is CD1D p.Trp49Arg (c.145T>C) pathogenic?

CD1D p.Trp49Arg (c.145T>C) is classified Likely benign in CD1D (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-14). AlphaMissense: ambiguous (0.5255); Rare (popmax 0.308%, afr).

How common is CD1D p.Trp49Arg (c.145T>C) in the general population?

CD1D p.Trp49Arg (c.145T>C) is rare (popmax 0.308%, afr) (gnomAD).

What do computational predictors say about CD1D p.Trp49Arg (c.145T>C)?

AlphaMissense predicts ambiguous (score 0.5255) — an in-silico prediction, not a clinical call.

CD1D p.Trp49Arg

c.145T>C · rs147976430 · VCV724721

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5255 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.308%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5255	ambiguous
REVEL	0.155	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP 1.9, phastCons 0.005
Regional constraint	o/e 1.05	unconstrained · MANE · 3,045 bp · p 0.31 · regional, not allelic
Overall
CADD	22.7	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 0.308% African / African-American · 231/74,968 alleles

Filtering AF 0.275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.263%

Overall 0.017% 274/1,613,960 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.308%	325
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.0233%	4,287
Middle Eastern	0.0165%	6,060
South Asian	0.00549%	18,214
European (non-Finnish)	8.47e-05%	1,179,967

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.Trp49Arg
Coding: c.145T>C
MANE Select: NM_001371762
dbSNP: rs147976430
Type: single nucleotide variant
Location: chr1:158181538 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.20 · 23 PDB
Residue 49: 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-trp49arg (accessed [today's date]).

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