Is DPPA5 p.Val28Ile (c.82G>A) pathogenic?

DPPA5 p.Val28Ile (c.82G>A) is classified Uncertain significance in DPPA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.1591); Rare (popmax 0.266%, afr).

How common is DPPA5 p.Val28Ile (c.82G>A) in the general population?

DPPA5 p.Val28Ile (c.82G>A) is rare (popmax 0.266%, afr) (gnomAD).

What do computational predictors say about DPPA5 p.Val28Ile (c.82G>A)?

AlphaMissense predicts likely benign (score 0.1591) — an in-silico prediction, not a clinical call.

DPPA5 p.Val28Ile

c.82G>A · VCV4662022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1591 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.266%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1591	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -6.68	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 1.1	GERP 0.83, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 902 bp · p 0.11 · regional, not allelic
Overall
CADD	16.29	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 0.266% African / African-American · 200/75,052 alleles

Filtering AF 0.236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.225%

Overall 0.0147% 238/1,614,214 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.266%	375
Middle Eastern	0.066%	1,516
Admixed American	0.01%	10,004
Remaining individualsnot grpmax-eligible	0.0064%	15,628
European (non-Finnish)	0.00203%	49,169

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.Val28Ile
Coding: c.82G>A
MANE Select: NM_001025290
Type: single nucleotide variant
Location: chr6:73354144 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.63
Residue 28: the kh; atypical domain

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

Similar variants

DPPA5 p.Val28Gly Uncertain significance ★ ⚠ same residue
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

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-val28ile (accessed [today's date]).

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