Is DPPA2 p.Arg131Trp (c.391C>T) pathogenic?

DPPA2 p.Arg131Trp (c.391C>T) is classified Uncertain significance in DPPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0911); Ultra-rare (popmax 0.0245%, eas).

How common is DPPA2 p.Arg131Trp (c.391C>T) in the general population?

DPPA2 p.Arg131Trp (c.391C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about DPPA2 p.Arg131Trp (c.391C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

DPPA2 p.Arg131Trp

c.391C>T · VCV4244560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.34	donor loss, 35 bp away · masked 0 · deltas
Pangolin	Δ0.23	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.3	GERP -3.5
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	13.28	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

Grpmax group 0.0245% East Asian · 11/44,896 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00291% 47/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
European (non-Finnish)	0.00305%	32,779

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: DPPA2
Protein: p.Arg131Trp
Coding: c.391C>T
MANE Select: NM_138815
Type: single nucleotide variant
Location: chr3:109309031 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.63
Residue 131: a UniProt-annotated variant site (in)

Full DPPA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPPA2 p.Arg131Gln Benign ★★ same residue
DPPA2 p.Leu278Ser Likely pathogenic ★ same type
DPPA2 p.Arg142Thr Uncertain significance ★ ⚠ same type
DPPA2 p.Arg145Gln Uncertain significance ★ ⚠ same type
DPPA2 p.Arg150Cys Uncertain significance ★ ⚠ same type
DPPA2 p.Arg150His Uncertain significance ★ ⚠ same type
DPPA2 p.Arg240His Uncertain significance ★ ⚠ same type
DPPA2 p.Arg97Gln 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/dppa2-p-arg131trp (accessed [today's date]).

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