Is DPPA5 p.Val28Gly (c.83T>G) pathogenic?

DPPA5 p.Val28Gly (c.83T>G) is classified Uncertain significance in DPPA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: ambiguous (0.3758); Ultra-rare (popmax 0.0187%, afr).

How common is DPPA5 p.Val28Gly (c.83T>G) in the general population?

DPPA5 p.Val28Gly (c.83T>G) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about DPPA5 p.Val28Gly (c.83T>G)?

AlphaMissense predicts ambiguous (score 0.3758) — an in-silico prediction, not a clinical call.

DPPA5 p.Val28Gly

c.83T>G · VCV3505030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Computational evidence

Protein change
AlphaMissense	0.3758	ambiguous
REVEL	0.415	indeterminate
SaProt	LLR -14.12	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.74, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 902 bp · p 0.11 · regional, not allelic
Overall
CADD	21.3	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 0.0187% African / African-American · 14/74,940 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.000929% 15/1,614,084 alleles · ultra-rare exomes 4/1,461,890 · genomes 11/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,353
European (non-Finnish)	8.47e-05%	1,180,050

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.Val28Gly
Coding: c.83T>G
MANE Select: NM_001025290
Type: single nucleotide variant
Location: chr6:73354143 (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.Val28Ile 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-val28gly (accessed [today's date]).

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