Is DPH1 p.Pro217His (c.650C>A) pathogenic?

DPH1 p.Pro217His (c.650C>A) is classified Uncertain significance in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.7959); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with DPH1 p.Pro217His (c.650C>A)?

DPH1 p.Pro217His (c.650C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPH1 p.Pro217His (c.650C>A) in the general population?

DPH1 p.Pro217His (c.650C>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DPH1 p.Pro217His (c.650C>A)?

AlphaMissense predicts likely pathogenic (score 0.7959) — an in-silico prediction, not a clinical call.

DPH1 p.Pro217His

c.650C>A · VCV3504873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7959	likely pathogenic
REVEL	0.402	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.074 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P222H vs ClinVar P217H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,988 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,506 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: DPH1
Protein: p.Pro217His
Coding: c.650C>A
MANE Select: NM_001383
Type: single nucleotide variant
Location: chr17:2036926 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.00

Full DPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH1 p.Arg144Trp Uncertain significance ★★ ⚠ same condition
DPH1 p.Ile241Phe Uncertain significance ★★ same condition
DPH1 p.Lys38Thr Likely benign ★★ same condition
DPH1 c.279-5C>T Uncertain significance ★ same condition
DPH1 c.558+4G>C Uncertain significance ★ same condition
DPH1 c.-12C>T Uncertain significance ★ ⚠ same condition
DPH1 c.-2T>A Uncertain significance ★ ⚠ same condition
DPH1 c.-6C>G 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/dph1-p-pro217his (accessed [today's date]).

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