Is GDPGP1 p.Arg102Pro (c.305G>C) pathogenic?

GDPGP1 p.Arg102Pro (c.305G>C) is classified Uncertain significance in GDPGP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely pathogenic (0.9413); Ultra-rare (popmax 0.0426%, afr).

How common is GDPGP1 p.Arg102Pro (c.305G>C) in the general population?

GDPGP1 p.Arg102Pro (c.305G>C) is ultra-rare (popmax 0.0426%, afr) (gnomAD).

What do computational predictors say about GDPGP1 p.Arg102Pro (c.305G>C)?

AlphaMissense predicts likely pathogenic (score 0.9413) — an in-silico prediction, not a clinical call.

GDPGP1 p.Arg102Pro

c.305G>C · rs375372924 · VCV3099320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9413 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0426%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9413	likely pathogenic
REVEL	0.698	pathogenic-leaning
SaProt	LLR -17.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,154 bp · p 0.061 · regional, not allelic
Overall
CADD	26.4	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

Grpmax group 0.0426% African / African-American · 32/75,052 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00229% 37/1,614,148 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0426%	2,345
Admixed American	0.00333%	30,010
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	8.47e-05%	1,180,020

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: GDPGP1
Protein: p.Arg102Pro
Coding: c.305G>C
MANE Select: NM_006384 · reported on NM_001013657
dbSNP: rs375372924
Type: single nucleotide variant
Location: chr15:90241213 (GRCh38)

Full GDPGP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/gdpgp1-p-arg102pro (accessed [today's date]).

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