Is GPD2 p.Cys45= (c.135C>T) pathogenic?

GPD2 p.Cys45= (c.135C>T) is classified Likely benign in GPD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-19). Very rare (popmax 6.2e-05%); Associated with GPD2-related disorder.

What condition is associated with GPD2 p.Cys45= (c.135C>T)?

GPD2 p.Cys45= (c.135C>T) is associated with GPD2-related disorder (ClinVar).

How common is GPD2 p.Cys45= (c.135C>T) in the general population?

GPD2 p.Cys45= (c.135C>T) is very rare (popmax 6.2e-05%) (gnomAD).

GPD2 p.Cys45=

c.135C>T · rs2468519467 · VCV3048119

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

GPD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor loss, 32 bp away · masked 0 · deltas
Pangolin	Δ0.35	gain · loss 0.27 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP -1.1	GERP -0.83
Overall
CADD	3.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,040 alleles · very rare exomes 1/1,460,764 · genomes 0/152,276 · joint denominator

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: GPD2
Protein: p.Cys45=
Coding: c.135C>T
MANE Select: NM_000408
dbSNP: rs2468519467
Type: single nucleotide variant
Location: chr2:156496076 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.47

Full GPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GPD2-related disorder

Similar variants

GPD2 c.497+5G>A Uncertain significance ★ same condition
GPD2 p.Leu576Val Likely benign same condition
GPD2 p.Pro408= Likely benign same condition
GPD2 p.Tyr193= Likely benign same condition
GPD2 p.Val194Ile Benign same condition
GPD2 p.Asn224Lys Uncertain significance ★★ ⚠ same type
GPD2 p.Ile308Val Likely benign ★★ same type
GPD2 p.Ala233Pro 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/gpd2-p-cys45 (accessed [today's date]).

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