Is CD1D p.Pro22Arg (c.65C>G) pathogenic?

CD1D p.Pro22Arg (c.65C>G) is classified Uncertain significance in CD1D (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely benign (0.0888); Absent from gnomAD v4.1.

How common is CD1D p.Pro22Arg (c.65C>G) in the general population?

CD1D p.Pro22Arg (c.65C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD1D p.Pro22Arg (c.65C>G)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

CD1D p.Pro22Arg

c.65C>G · rs1648407123 · VCV2260709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -3.3
Regional constraint	o/e 1.05	unconstrained · MANE · 3,045 bp · p 0.31 · regional, not allelic
Overall
CADD	9.55	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD1D
Protein: p.Pro22Arg
Coding: c.65C>G
MANE Select: NM_001371762
dbSNP: rs1648407123
Type: single nucleotide variant
Location: chr1:158181458 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.20 · 23 PDB

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-pro22arg (accessed [today's date]).

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