Is DPH2 p.Gln308Ter (c.922C>T) pathogenic?

DPH2 p.Gln308Ter (c.922C>T) is classified Uncertain significance in DPH2 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-06-04). Very rare (popmax 0.00161%, nfe); Associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2.

How common is DPH2 p.Gln308Ter (c.922C>T) in the general population?

DPH2 p.Gln308Ter (c.922C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

DPH2 p.Gln308Ter

Q: What condition is associated with DPH2 p.Gln308Ter (c.922C>T)?

DPH2 p.Gln308Ter (c.922C>T) is associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2 (ClinVar).

c.922C>T · rs755058688 · VCV872918

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -1.9, phastCons 0.003
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,056 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,612,998 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,108
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: DPH2
Protein: p.Gln308Ter
Coding: c.922C>T
MANE Select: NM_001384
dbSNP: rs755058688
Type: single nucleotide variant
Location: chr1:43971824 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60
Residue 308: a UniProt-annotated variant site (in dedssh2; severely impairs diphthamide modification of elongation factor 2)

Full DPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental delay with short stature, dysmorphic facial features, and sparse hair 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH2 p.Arg477Ter Likely pathogenic ★ same condition
DPH2 p.Ser75Ter Likely pathogenic ★ same condition
DPH2 p.Arg201Cys Uncertain significance ★ ⚠ same condition
DPH2 p.Arg282fs Conflicting classifications of pathogenicity ★ same condition
DPH2 p.Arg201His Uncertain significance ★★ ⚠ same type
DPH2 p.Ala310Val Uncertain significance ★ ⚠ same type
DPH2 p.Ala345Thr Uncertain significance ★ ⚠ same type
DPH2 p.Ala448Thr 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/dph2-p-gln308ter (accessed [today's date]).

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