Is DPPA4 p.Pro166Leu (c.497C>T) pathogenic?

DPPA4 p.Pro166Leu (c.497C>T) is classified Uncertain significance in DPPA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.085); Absent from gnomAD v4.1.

How common is DPPA4 p.Pro166Leu (c.497C>T) in the general population?

DPPA4 p.Pro166Leu (c.497C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPPA4 p.Pro166Leu (c.497C>T)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

DPPA4 p.Pro166Leu

c.497C>T · VCV4014677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.34	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 0.81	GERP -2.4
Regional constraint	o/e 1.03	unconstrained · MANE · 2,820 bp · p 0.7 · regional, not allelic
Overall
CADD	11.47	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPPA4
Protein: p.Pro166Leu
Coding: c.497C>T
MANE Select: NM_018189
Type: single nucleotide variant
Location: chr3:109330706 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.05
Residue 166: the 'disordered' region

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.Ala201Pro 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

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-pro166leu (accessed [today's date]).

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