Is DPPA5 p.Pro12Ser (c.34C>T) pathogenic?

DPPA5 p.Pro12Ser (c.34C>T) is classified Uncertain significance in DPPA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1642); Very rare (popmax 0.00891%, eas).

How common is DPPA5 p.Pro12Ser (c.34C>T) in the general population?

DPPA5 p.Pro12Ser (c.34C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DPPA5 p.Pro12Ser (c.34C>T)?

AlphaMissense predicts likely benign (score 0.1642) — an in-silico prediction, not a clinical call.

DPPA5 p.Pro12Ser

c.34C>T · VCV4244586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1642	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.27, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 902 bp · p 0.11 · regional, not allelic
Overall
CADD	15.34	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 0.00891% East Asian · 4/44,872 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,461,878 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: DPPA5
Protein: p.Pro12Ser
Coding: c.34C>T
MANE Select: NM_001025290
Type: single nucleotide variant
Location: chr6:73354192 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.63

Full DPPA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPPA5 p.Ala108Gly Uncertain significance ★ ⚠ same type
DPPA5 p.Arg43Gly Uncertain significance ★ ⚠ same type
DPPA5 p.Arg92His Uncertain significance ★ ⚠ same type
DPPA5 p.Arg94His Uncertain significance ★ ⚠ same type
DPPA5 p.Asn107Lys Uncertain significance ★ ⚠ same type
DPPA5 p.Leu109Pro Uncertain significance ★ ⚠ same type
DPPA5 p.Leu78Val Uncertain significance ★ ⚠ same type
DPPA5 p.Lys101Arg 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/dppa5-p-pro12ser (accessed [today's date]).

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