Is DPPA5 p.Pro39Leu (c.116C>T) pathogenic?

DPPA5 p.Pro39Leu (c.116C>T) is classified Uncertain significance in DPPA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: likely benign (0.1959); Very rare (popmax 0.00167%, amr).

How common is DPPA5 p.Pro39Leu (c.116C>T) in the general population?

DPPA5 p.Pro39Leu (c.116C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPPA5 p.Pro39Leu (c.116C>T)?

AlphaMissense predicts likely benign (score 0.1959) — an in-silico prediction, not a clinical call.

DPPA5 p.Pro39Leu

c.116C>T · rs1238480576 · VCV2268890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1959	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.49	GERP -3, phastCons 0.1
Regional constraint	o/e 0.87	unconstrained · MANE · 902 bp · p 0.11 · regional, not allelic
Overall
CADD	11.84	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

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000616% 9/1,461,612 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
Remaining individualsnot grpmax-eligible	0.0048%	20,831
Admixed Americangrpmax	0.00167%	60,000
European (non-Finnish)	0.00017%	589,904

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DPPA5
Protein: p.Pro39Leu
Coding: c.116C>T
MANE Select: NM_001025290
dbSNP: rs1238480576
Type: single nucleotide variant
Location: chr6:73354029 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.63
Residue 39: the kh; atypical domain

Full DPPA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPPA5 p.Ala108Gly Uncertain significance ★ ⚠ same type
DPPA5 p.Arg43Gly Uncertain significance ★ ⚠ same type
DPPA5 p.Arg92His Uncertain significance ★ ⚠ same type
DPPA5 p.Arg94His Uncertain significance ★ ⚠ same type
DPPA5 p.Asn107Lys Uncertain significance ★ ⚠ same type
DPPA5 p.Leu109Pro Uncertain significance ★ ⚠ same type
DPPA5 p.Leu78Val Uncertain significance ★ ⚠ same type
DPPA5 p.Lys101Arg 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/dppa5-p-pro39leu (accessed [today's date]).

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