Is DPH1 p.Val257= (c.771C>A) pathogenic?

DPH1 p.Val257= (c.771C>A) is classified Likely benign in DPH1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-21). Very rare (popmax 0.000678%, nfe); Associated with DPH1-related disorder.

What condition is associated with DPH1 p.Val257= (c.771C>A)?

DPH1 p.Val257= (c.771C>A) is associated with DPH1-related disorder (ClinVar).

How common is DPH1 p.Val257= (c.771C>A) in the general population?

DPH1 p.Val257= (c.771C>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

DPH1 p.Val257=

c.771C>A · rs1280854549 · VCV3052826

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

DPH1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.084	GERP -2.2, phastCons 0.034
Overall
CADD	4.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,028 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000616% 9/1,461,754 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	0.000678%	147,504

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val257=
Coding: c.771C>A
MANE Select: NM_001383
dbSNP: rs1280854549
Type: single nucleotide variant
Location: chr17:2040239 (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

DPH1-related disorder

Similar variants

DPH1 p.Met1Lys Likely pathogenic ★ ⚠ same condition
DPH1 p.Lys38= Likely benign same condition
DPH1 p.Ser183= Benign same condition
DPH1 p.Tyr128= Likely benign same condition
DPH1 p.Leu229Pro Pathogenic/Likely pathogenic ★★ same type
DPH1 p.Arg144Trp Uncertain significance ★★ ⚠ same type
DPH1 p.Arg22Gln Uncertain significance ★★ ⚠ same type
DPH1 p.Arg27His 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/dph1-p-val257 (accessed [today's date]).

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