Is DPPA4 p.Ala201Pro (c.601G>C) pathogenic?

DPPA4 p.Ala201Pro (c.601G>C) is classified Uncertain significance in DPPA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely pathogenic (0.7639); Very rare (popmax 0.00167%, amr).

How common is DPPA4 p.Ala201Pro (c.601G>C) in the general population?

DPPA4 p.Ala201Pro (c.601G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPPA4 p.Ala201Pro (c.601G>C)?

AlphaMissense predicts likely pathogenic (score 0.7639) — an in-silico prediction, not a clinical call.

DPPA4 p.Ala201Pro

c.601G>C · VCV3505028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7639	likely pathogenic
REVEL	0.279	benign-leaning
SaProt	LLR -9.47	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 0.025	GERP -4.2, phastCons 0.75
Regional constraint	o/e 1.03	unconstrained · MANE · 2,820 bp · p 0.7 · regional, not allelic
Overall
CADD	20.9	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 0.00167% Admixed American · 1/60,022 alleles

Overall 6.84e-05% 1/1,461,894 alleles · very rare

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: DPPA4
Protein: p.Ala201Pro
Coding: c.601G>C
MANE Select: NM_018189
Type: single nucleotide variant
Location: chr3:109330602 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.05

Full DPPA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPPA4 p.Ala139Thr Uncertain significance ★ ⚠ same type
DPPA4 p.Asn181His Uncertain significance ★ ⚠ same type
DPPA4 p.Asn34Asp Uncertain significance ★ ⚠ same type
DPPA4 p.Gln146Arg Uncertain significance ★ ⚠ same type
DPPA4 p.Gln223Lys Uncertain significance ★ ⚠ same type
DPPA4 p.Glu262Lys Uncertain significance ★ ⚠ same type
DPPA4 p.Gly174Arg Uncertain significance ★ ⚠ same type
DPPA4 p.His95Asn 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/dppa4-p-ala201pro (accessed [today's date]).

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