Is DPPA3 p.Arg108Cys (c.322C>T) pathogenic?

DPPA3 p.Arg108Cys (c.322C>T) is classified Uncertain significance in DPPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1516); Very rare (popmax 0.00167%, amr).

How common is DPPA3 p.Arg108Cys (c.322C>T) in the general population?

DPPA3 p.Arg108Cys (c.322C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPPA3 p.Arg108Cys (c.322C>T)?

AlphaMissense predicts likely benign (score 0.1516) — an in-silico prediction, not a clinical call.

DPPA3 p.Arg108Cys

c.322C>T · VCV4244573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1516	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.87 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.2	GERP -1.6
Regional constraint	o/e 0.76	unconstrained · MANE · 5,503 bp · p 0.00084 · regional, not allelic
Overall
CADD	4.825	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 0.00167% Admixed American · 1/59,948 alleles

Overall 0.000124% 2/1,613,790 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,948
European (non-Finnish)	8.47e-05%	1,179,979

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: DPPA3
Protein: p.Arg108Cys
Coding: c.322C>T
MANE Select: NM_199286
Type: single nucleotide variant
Location: chr12:7715422 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.46 · 3 PDB

Full DPPA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPPA3 p.Ala147Val Uncertain significance ★ ⚠ same type
DPPA3 p.Arg24Trp Uncertain significance ★ ⚠ same type
DPPA3 p.Arg62Gly Uncertain significance ★ ⚠ same type
DPPA3 p.Arg83Gly Uncertain significance ★ ⚠ same type
DPPA3 p.Arg98Ser Uncertain significance ★ ⚠ same type
DPPA3 p.Asn116Asp Uncertain significance ★ ⚠ same type
DPPA3 p.Asn151Ser Uncertain significance ★ ⚠ same type
DPPA3 p.Gln158Arg 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/dppa3-p-arg108cys (accessed [today's date]).

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