Is DPH2 p.His302Asn (c.904C>A) pathogenic?

DPH2 p.His302Asn (c.904C>A) is classified Uncertain significance in DPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: ambiguous (0.3652); Ultra-rare (popmax 0.0332%, nfe).

How common is DPH2 p.His302Asn (c.904C>A) in the general population?

DPH2 p.His302Asn (c.904C>A) is ultra-rare (popmax 0.0332%, nfe) (gnomAD).

What do computational predictors say about DPH2 p.His302Asn (c.904C>A)?

AlphaMissense predicts ambiguous (score 0.3652) — an in-silico prediction, not a clinical call.

DPH2 p.His302Asn

c.904C>A · rs765854839 · VCV2468534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3652 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3652	ambiguous
REVEL	0.156	moderately benign-leaning
SaProt	LLR -11.69	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,712 bp · p 0.054 · regional, not allelic
Overall
CADD	24.6	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

Grpmax group 0.0332% European (non-Finnish) · 392/1,180,044 alleles

Filtering AF 0.0304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.0259% 418/1,611,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0332%	3,010
Remaining individualsnot grpmax-eligible	0.0272%	3,675
African / African-American	0.0107%	9,368
Admixed American	0.00167%	60,018

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.His302Asn
Coding: c.904C>A
MANE Select: NM_001384
dbSNP: rs765854839
Type: single nucleotide variant
Location: chr1:43971806 (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

Similar variants

DPH2 p.His302= Likely benign ★ same residue
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

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-his302asn (accessed [today's date]).

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