Is DPPA3 p.Trp141Arg (c.421T>C) pathogenic?

DPPA3 p.Trp141Arg (c.421T>C) is classified Uncertain significance in DPPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely pathogenic (0.8608); Very rare (popmax 0.00881%, nfe).

How common is DPPA3 p.Trp141Arg (c.421T>C) in the general population?

DPPA3 p.Trp141Arg (c.421T>C) is very rare (popmax 0.00881%, nfe) (gnomAD).

What do computational predictors say about DPPA3 p.Trp141Arg (c.421T>C)?

AlphaMissense predicts likely pathogenic (score 0.8608) — an in-silico prediction, not a clinical call.

DPPA3 p.Trp141Arg

c.421T>C · rs201591750 · VCV2347852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00881%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8608	likely pathogenic · top 1% in DPPA3
REVEL	0.088	moderately benign-leaning
SaProt	LLR -4.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.1, phastCons 0.97
Regional constraint	o/e 0.76	unconstrained · MANE · 5,503 bp · p 0.00084 · regional, not allelic
Overall
CADD	19.78	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 0.00881% European (non-Finnish) · 104/1,179,984 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00669% 108/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00881%	11,346
Remaining individualsnot grpmax-eligible	0.0048%	20,834
African / African-American	0.00133%	75,004

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.Trp141Arg
Coding: c.421T>C
MANE Select: NM_199286
dbSNP: rs201591750
Type: single nucleotide variant
Location: chr12:7717018 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.46 · 3 PDB
Residue 141: the 'disordered' region

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-trp141arg (accessed [today's date]).

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