Is DPPA2 p.Leu143Ser (c.428T>C) pathogenic?

DPPA2 p.Leu143Ser (c.428T>C) is classified Uncertain significance in DPPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1692); Ultra-rare (popmax 0.0559%, afr).

How common is DPPA2 p.Leu143Ser (c.428T>C) in the general population?

DPPA2 p.Leu143Ser (c.428T>C) is ultra-rare (popmax 0.0559%, afr) (gnomAD).

What do computational predictors say about DPPA2 p.Leu143Ser (c.428T>C)?

AlphaMissense predicts likely benign (score 0.1692) — an in-silico prediction, not a clinical call.

DPPA2 p.Leu143Ser

c.428T>C · VCV4662009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1692 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0559%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1692	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.63	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 1.9	GERP 0.98
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	11.62	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 0.0559% African / African-American · 42/75,078 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00304% 49/1,614,250 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0559%	1,788
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.00167%	60,022
European (non-Finnish)	8.47e-05%	1,180,044

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.Leu143Ser
Coding: c.428T>C
MANE Select: NM_138815
Type: single nucleotide variant
Location: chr3:109308262 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.63

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

Similar variants

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
DPPA2 p.Arg240His 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-leu143ser (accessed [today's date]).

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