Is DPH1 p.Arg22= (c.66G>T) pathogenic?

DPH1 p.Arg22= (c.66G>T) is classified Likely benign in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.128%, amr).

How common is DPH1 p.Arg22= (c.66G>T) in the general population?

DPH1 p.Arg22= (c.66G>T) is rare (popmax 0.128%, amr) (gnomAD).

DPH1 p.Arg22=

c.66G>T · rs777742368 · VCV759153

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.128%, amr)

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 1.4	GERP -2.3, phastCons 0.35
Overall
CADD	1.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.128% Admixed American · 77/60,022 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0967%

Overall 0.00496% 80/1,614,016 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.128%	780
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00133%	75,042

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.Arg22=
Coding: c.66G>T
MANE Select: NM_001383
dbSNP: rs777742368
Type: single nucleotide variant
Location: chr17:2033509 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.00
Residue 22: the 'disordered' region

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

Similar variants

DPH1 p.Arg22Gln Uncertain significance ★★ ⚠ same residue
OVCA2 p.Phe22Leu Uncertain significance ★ ⚠ same residue
OVCA2 p.Phe22Ser Uncertain significance ★ ⚠ same residue
DPH1 p.Leu229Pro Pathogenic/Likely pathogenic ★★ same type
DPH1 p.Arg144Trp Uncertain significance ★★ ⚠ same type
DPH1 p.Arg27His Uncertain significance ★★ ⚠ same type
DPH1 p.Arg47Trp Uncertain significance ★★ ⚠ same type
DPH1 p.Asp231Glu 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-arg22 (accessed [today's date]).

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