Is DPPA2 p.Cys96Ser (c.287G>C) pathogenic?

DPPA2 p.Cys96Ser (c.287G>C) is classified Likely benign in DPPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1353); Very rare (popmax 0.000205%).

How common is DPPA2 p.Cys96Ser (c.287G>C) in the general population?

DPPA2 p.Cys96Ser (c.287G>C) is very rare (popmax 0.000205%) (gnomAD).

What do computational predictors say about DPPA2 p.Cys96Ser (c.287G>C)?

AlphaMissense predicts likely benign (score 0.1353) — an in-silico prediction, not a clinical call.

DPPA2 p.Cys96Ser

c.287G>C · VCV3505020

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1353 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000205%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1353	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -4.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.42	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.019	GERP -2.9
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	0.233	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000205%

Overall 0.000205% 3/1,461,892 alleles · very rare

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.Cys96Ser
Coding: c.287G>C
MANE Select: NM_138815
Type: single nucleotide variant
Location: chr3:109309225 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.63
Residue 96: the sap domain

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

Similar variants

DPPA2 p.Cys96Arg Uncertain significance ★ ⚠ same residue
DPPA2 p.Arg131Gln Benign ★★ same type
DPPA2 p.Leu278Ser Likely pathogenic ★ same type
DPPA2 p.Arg131Trp Uncertain significance ★ ⚠ 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

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-cys96ser (accessed [today's date]).

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