Is DPPA2 p.Phe243Cys (c.728T>G) pathogenic?

DPPA2 p.Phe243Cys (c.728T>G) is classified Uncertain significance in DPPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.8075); Very rare (popmax 0.00446%, eas).

How common is DPPA2 p.Phe243Cys (c.728T>G) in the general population?

DPPA2 p.Phe243Cys (c.728T>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DPPA2 p.Phe243Cys (c.728T>G)?

AlphaMissense predicts likely pathogenic (score 0.8075) — an in-silico prediction, not a clinical call.

DPPA2 p.Phe243Cys

c.728T>G · VCV4244563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8075	likely pathogenic · top 7% in DPPA2
REVEL	0.379	indeterminate
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	24.6	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 0.00446% East Asian · 2/44,858 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000124% 2/1,614,076 alleles · very rare exomes 2/1,461,828 · genomes 0/152,248 · joint denominator

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.Phe243Cys
Coding: c.728T>G
MANE Select: NM_138815
Type: single nucleotide variant
Location: chr3:109304601 (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.Phe243Ser Uncertain significance ★ ⚠ same residue
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

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-phe243cys (accessed [today's date]).

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