Is DPH5 p.Asp244fs (c.728_729dup) pathogenic?

DPH5 p.Asp244fs (c.728729dup) is classified Uncertain significance in DPH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). Very rare (popmax 0.00267%, afr); Associated with neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties.

How common is DPH5 p.Asp244fs (c.728_729dup) in the general population?

DPH5 p.Asp244fs (c.728_729dup) is very rare (popmax 0.00267%, afr) (gnomAD).

DPH5 p.Asp244fs

Q: What condition is associated with DPH5 p.Asp244fs (c.728_729dup)?

DPH5 p.Asp244fs (c.728_729dup) is associated with neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties (ClinVar).

c.728_729dup · VCV3779282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,032 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000137% 2/1,461,864 alleles · very rare

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: DPH5
Protein: p.Asp244fs
Coding: c.728_729dup
MANE Select: NM_015958
Type: Microsatellite
Location: chr1:100990536 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20
Residue 244: a UniProt-annotated variant site (in nedsff; loss of function in diphthamide biosynthesis shown in a yeast assay system)

Full DPH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH5 p.Asp244Asn Uncertain significance ★ ⚠ same residue
DPH5 p.His260Arg Pathogenic/Likely pathogenic ★★ same condition
DPH5 p.Pro104Thr Uncertain significance ★★ ⚠ same condition
DPH5 c.260+1G>T Likely pathogenic ★ same condition
DPH5 p.Ala223Val Uncertain significance ★ ⚠ same condition
DPH5 p.Arg224Ser Uncertain significance ★ ⚠ same condition
DPH5 p.Leu163Pro Uncertain significance ★ ⚠ same condition
DPH5 p.Leu7Phe Uncertain significance ★ ⚠ same condition

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/dph5-p-asp244fs (accessed [today's date]).

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