Is GPD1 p.Trp14Arg (c.40T>A) pathogenic?

GPD1 p.Trp14Arg (c.40T>A) is classified Uncertain significance in GPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.9947); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GPD1 p.Trp14Arg (c.40T>A)?

GPD1 p.Trp14Arg (c.40T>A) is associated with Inborn genetic diseases (ClinVar).

How common is GPD1 p.Trp14Arg (c.40T>A) in the general population?

GPD1 p.Trp14Arg (c.40T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPD1 p.Trp14Arg (c.40T>A)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

GPD1 p.Trp14Arg

c.40T>A · VCV4265538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic · top 2% in GPD1
REVEL	0.644	pathogenic-leaning
SaProt	LLR -15.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,465 bp · p 0.4 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: GPD1
Protein: p.Trp14Arg
Coding: c.40T>A
MANE Select: NM_005276
Type: single nucleotide variant
Location: chr12:50104090 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.39 · 7 PDB
Residue 14: a binding site; an α-helix

Full GPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GPD1 p.Trp14Ter Likely pathogenic ★ same residue
GPD1 p.Ala202Val Uncertain significance ★★ ⚠ same condition
GPD1 p.Arg271Gln Uncertain significance ★★ ⚠ same condition
GPD1 p.Arg35Gln Uncertain significance ★★ ⚠ same condition
GPD1 p.Glu301Lys Uncertain significance ★★ ⚠ same condition
GPD1 p.Glu331Lys Uncertain significance ★★ ⚠ same condition
GPD1 p.Gly267Arg Uncertain significance ★★ ⚠ same condition
GPD1 p.Lys240Gln Uncertain significance ★★ ⚠ same condition

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/gpd1-p-trp14arg (accessed [today's date]).

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