Is DPPA5 p.Gly72Ser (c.214G>A) pathogenic?

DPPA5 p.Gly72Ser (c.214G>A) is classified Uncertain significance in DPPA5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-16). AlphaMissense: likely benign (0.3394); Absent from gnomAD v4.1; Associated with Hirschsprung disease.

What condition is associated with DPPA5 p.Gly72Ser (c.214G>A)?

DPPA5 p.Gly72Ser (c.214G>A) is associated with Hirschsprung disease (ClinVar).

How common is DPPA5 p.Gly72Ser (c.214G>A) in the general population?

DPPA5 p.Gly72Ser (c.214G>A) is absent from gnomAD v4.1 (gnomAD).

How is Hirschsprung disease inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DPPA5 p.Gly72Ser (c.214G>A)?

AlphaMissense predicts likely benign (score 0.3394) — an in-silico prediction, not a clinical call.

DPPA5 p.Gly72Ser

c.214G>A · rs1582614694 · VCV691396

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3394 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Hirschsprung disease

Computational evidence

Protein change
AlphaMissense	0.3394	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.82, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 902 bp · p 0.11 · regional, not allelic
Overall
CADD	16.01	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: DPPA5
Protein: p.Gly72Ser
Coding: c.214G>A
MANE Select: NM_001025290
dbSNP: rs1582614694
Type: single nucleotide variant
Location: chr6:73353931 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.63
Residue 72: the kh; atypical domain

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

Disease context

Hirschsprung disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hirschsprung disease (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Multigenic/multifactorial
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

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-gly72ser (accessed [today's date]).

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