Is DPH2 p.Ser75Ter (c.224C>G) pathogenic?

DPH2 p.Ser75Ter (c.224C>G) is classified Likely pathogenic in DPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Absent from gnomAD v4.1; Associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2.

How common is DPH2 p.Ser75Ter (c.224C>G) in the general population?

DPH2 p.Ser75Ter (c.224C>G) is absent from gnomAD v4.1 (gnomAD).

DPH2 p.Ser75Ter

Q: What condition is associated with DPH2 p.Ser75Ter (c.224C>G)?

DPH2 p.Ser75Ter (c.224C>G) is associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2 (ClinVar).

c.224C>G · rs2529100401 · VCV2671662

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2 of 6
REVEL	0.073	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.88 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Overall
CADD	37.0	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

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: DPH2
Protein: p.Ser75Ter
Coding: c.224C>G
MANE Select: NM_001384
dbSNP: rs2529100401
Type: single nucleotide variant
Location: chr1:43970672 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60

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.Ser75Pro Uncertain significance ★ ⚠ same residue
DPH2 p.Arg477Ter Likely pathogenic ★ same condition
DPH2 p.Arg201Cys Uncertain significance ★ ⚠ same condition
DPH2 p.Gln308Ter 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

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-ser75ter (accessed [today's date]).

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