Is DPH2 p.Ser87Ile (c.260G>T) pathogenic?

DPH2 p.Ser87Ile (c.260G>T) is classified Uncertain significance in DPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-16). AlphaMissense: ambiguous (0.4109); Absent from gnomAD v4.1; Associated with Macrocephaly.

What condition is associated with DPH2 p.Ser87Ile (c.260G>T)?

DPH2 p.Ser87Ile (c.260G>T) is associated with Macrocephaly, intellectual disability (ClinVar).

How common is DPH2 p.Ser87Ile (c.260G>T) in the general population?

DPH2 p.Ser87Ile (c.260G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPH2 p.Ser87Ile (c.260G>T)?

AlphaMissense predicts ambiguous (score 0.4109) — an in-silico prediction, not a clinical call.

DPH2 p.Ser87Ile

c.260G>T · rs1571781453 · VCV694731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4109 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Macrocephaly

Computational evidence

Protein change
AlphaMissense	0.4109	ambiguous
REVEL	0.628	indeterminate
SaProt	LLR -12.31	damaging
Splicing
SpliceAI	Δ0.95	donor loss · deltas
Pangolin	Δ0.81	loss · gain 0.56 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,712 bp · p 0.054 · regional, not allelic
Overall
CADD	36.0	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

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.Ser87Ile
Coding: c.260G>T
MANE Select: NM_001384
dbSNP: rs1571781453
Type: single nucleotide variant
Location: chr1:43970708 (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

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

Also linked: intellectual disability

Similar variants

DPH2 p.Arg201His Uncertain significance ★★ ⚠ same type
DPH2 p.Arg477Ter Likely pathogenic ★ same type
DPH2 p.Ser75Ter Likely pathogenic ★ same type
DPH2 p.Ala310Val Uncertain significance ★ ⚠ same type
DPH2 p.Ala345Thr Uncertain significance ★ ⚠ same type
DPH2 p.Ala448Thr Uncertain significance ★ ⚠ same type
DPH2 p.Arg125His Uncertain significance ★ ⚠ same type
DPH2 p.Arg169Cys 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-ser87ile (accessed [today's date]).

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