Is DDRGK1 p.Arg142Pro (c.425G>C) pathogenic?

DDRGK1 p.Arg142Pro (c.425G>C) is classified Uncertain significance in DDRGK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-20). AlphaMissense: likely pathogenic (0.9912); Very rare (popmax 0.00167%, amr).

How common is DDRGK1 p.Arg142Pro (c.425G>C) in the general population?

DDRGK1 p.Arg142Pro (c.425G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DDRGK1 p.Arg142Pro (c.425G>C)?

AlphaMissense predicts likely pathogenic (score 0.9912) — an in-silico prediction, not a clinical call.

DDRGK1 p.Arg142Pro

c.425G>C · rs190574404 · VCV1973929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9912	likely pathogenic · top 1% in DDRGK1
REVEL	0.416	indeterminate
SaProt	LLR -15.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 14 kb · p 0.41 · 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

Grpmax group 0.00167% Admixed American · 1/59,982 alleles

Overall 0.000137% 2/1,461,498 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,982
European (non-Finnish)	8.47e-05%	1,179,942

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: DDRGK1
Protein: p.Arg142Pro
Coding: c.425G>C
MANE Select: NM_023935
dbSNP: rs190574404
Type: single nucleotide variant
Location: chr20:3200086 (GRCh38)
Gene constraint: LOEUF 1.213 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 8 PDB
Residue 142: an α-helix; the 'disordered' region; the 'mediates interaction with trip4' region

Full DDRGK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDRGK1 p.Arg142Cys Uncertain significance ★ ⚠ same residue
DDRGK1 p.Arg131Ter Pathogenic ★★ same type
DDRGK1 p.Ala29Val Uncertain significance ★★ ⚠ same type
DDRGK1 p.Ala95Gly Uncertain significance ★★ ⚠ same type
DDRGK1 p.Arg147Gln Uncertain significance ★★ ⚠ same type
DDRGK1 p.Arg241His Uncertain significance ★★ ⚠ same type
DDRGK1 p.Arg265Trp Uncertain significance ★★ ⚠ same type
DDRGK1 p.Arg27Gln 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/ddrgk1-p-arg142pro (accessed [today's date]).

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