Is DPPA3 p.Ala147Val (c.440C>T) pathogenic?

DPPA3 p.Ala147Val (c.440C>T) is classified Uncertain significance in DPPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: ambiguous (0.3687); Very rare (popmax 8.48e-05%, nfe).

How common is DPPA3 p.Ala147Val (c.440C>T) in the general population?

DPPA3 p.Ala147Val (c.440C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DPPA3 p.Ala147Val (c.440C>T)?

AlphaMissense predicts ambiguous (score 0.3687) — an in-silico prediction, not a clinical call.

DPPA3 p.Ala147Val

c.440C>T · rs752855109 · VCV3085596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3687	ambiguous
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.59	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -2.4, phastCons 0.001
Regional constraint	o/e 0.76	unconstrained · MANE · 5,503 bp · p 0.00084 · regional, not allelic
Overall
CADD	11.47	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 8.48e-05% European (non-Finnish) · 1/1,179,900 alleles

Overall 0.000658% 1/151,870 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: DPPA3
Protein: p.Ala147Val
Coding: c.440C>T
MANE Select: NM_199286
dbSNP: rs752855109
Type: single nucleotide variant
Location: chr12:7717037 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.46 · 3 PDB
Residue 147: the 'disordered' region

Full DPPA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
DPPA3 p.Gln158Arg 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-ala147val (accessed [today's date]).

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