Is DPPA2 p.Leu263Ser (c.788T>C) pathogenic?

DPPA2 p.Leu263Ser (c.788T>C) is classified Uncertain significance in DPPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely pathogenic (0.8267); Ultra-rare (popmax 0.0296%, sas).

How common is DPPA2 p.Leu263Ser (c.788T>C) in the general population?

DPPA2 p.Leu263Ser (c.788T>C) is ultra-rare (popmax 0.0296%, sas) (gnomAD).

What do computational predictors say about DPPA2 p.Leu263Ser (c.788T>C)?

AlphaMissense predicts likely pathogenic (score 0.8267) — an in-silico prediction, not a clinical call.

DPPA2 p.Leu263Ser

c.788T>C · rs145792733 · VCV2567037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8267 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8267	likely pathogenic · top 6% in DPPA2
REVEL	0.349	indeterminate
SaProt	LLR -4.28	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	24.4	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 0.0296% South Asian · 27/91,076 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0244%

Overall 0.0228% 368/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0296%	3,373
European (non-Finnish)	0.0279%	3,587
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00534%	18,729

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.Leu263Ser
Coding: c.788T>C
MANE Select: NM_138815
dbSNP: rs145792733
Type: single nucleotide variant
Location: chr3:109304541 (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-leu263ser (accessed [today's date]).

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