Is DPH1 p.Ser183= (c.549G>A) pathogenic?

DPH1 p.Ser183= (c.549G>A) is classified Benign in DPH1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-08). Common (popmax 12.4%, mid) — too common for a highly-penetrant pathogenic allele; Associated with DPH1-related disorder.

What condition is associated with DPH1 p.Ser183= (c.549G>A)?

DPH1 p.Ser183= (c.549G>A) is associated with DPH1-related disorder (ClinVar).

DPH1 p.Ser183=

Q: How common is DPH1 p.Ser183= (c.549G>A) in the general population?

DPH1 p.Ser183= (c.549G>A) is common (popmax 12.4%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.549G>A · rs61753099 · VCV3056642

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 12.4%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

DPH1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.51	GERP -4.6
Overall
CADD	10.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.4% Middle Eastern · 750/6,062 alleles

Filtering AF 11.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.3%

Overall 7.15% 115,347/1,613,962 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	15.4%	7
Middle Easterngrpmax	12.4%	8
European (non-Finnish)	8.13%	12
Remaining individualsnot grpmax-eligible	7.59%	13
Admixed American	4.67%	21
Amishnot grpmax-eligible	3.73%	27
South Asian	3.71%	27
Finnishnot grpmax-eligible	3.02%	33
African / African-American	1.67%	60
East Asian	0.0423%	2,363

Ashkenazi Jewish 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.Ser183=
Coding: c.549G>A
MANE Select: NM_001383
dbSNP: rs61753099
Type: single nucleotide variant
Location: chr17:2036677 (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

OVCA2 p.Pro183Ser Uncertain significance ★ ⚠ same residue
DPH1 p.Met1Lys Likely pathogenic ★ ⚠ same condition
DPH1 p.Lys38= Likely benign same condition
DPH1 p.Tyr128= Likely benign same condition
DPH1 p.Val257= 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

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-ser183 (accessed [today's date]).

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