Is DPPA3 p.Ser57Pro (c.169T>C) pathogenic?

DPPA3 p.Ser57Pro (c.169T>C) is classified Likely benign in DPPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.045); Very rare (popmax 0.0011%, sas).

How common is DPPA3 p.Ser57Pro (c.169T>C) in the general population?

DPPA3 p.Ser57Pro (c.169T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DPPA3 p.Ser57Pro (c.169T>C)?

AlphaMissense predicts likely benign (score 0.045) — an in-silico prediction, not a clinical call.

DPPA3 p.Ser57Pro

c.169T>C · VCV3842318

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.045	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.31	GERP -2.4
Regional constraint	o/e 0.76	unconstrained · MANE · 5,503 bp · p 0.00084 · regional, not allelic
Overall
CADD	0.229	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 0.0011% South Asian · 1/91,064 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,678 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,064
European (non-Finnish)	0.000254%	393,286

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.Ser57Pro
Coding: c.169T>C
MANE Select: NM_199286
Type: single nucleotide variant
Location: chr12:7715269 (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.Arg108Cys 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

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-ser57pro (accessed [today's date]).

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