Is DPH1 p.Arg47Gln (c.140G>A) pathogenic?

DPH1 p.Arg47Gln (c.140G>A) is classified Likely benign in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0537); Ultra-rare (popmax 0.0201%, eas); Associated with Inborn genetic diseases.

What condition is associated with DPH1 p.Arg47Gln (c.140G>A)?

DPH1 p.Arg47Gln (c.140G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPH1 p.Arg47Gln (c.140G>A) in the general population?

DPH1 p.Arg47Gln (c.140G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about DPH1 p.Arg47Gln (c.140G>A)?

AlphaMissense predicts likely benign (score 0.0537) — an in-silico prediction, not a clinical call.

DPH1 p.Arg47Gln

c.140G>A · rs202050177 · VCV3085462

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0537 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0537	likely benign
REVEL	0.017	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -0.95, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.074 · regional, not allelic
Overall
CADD	7.874	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 R52Q vs ClinVar R47Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,886 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00632% 102/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,692
East Asiangrpmax	0.0201%	4,987
Remaining individualsnot grpmax-eligible	0.0112%	8,927
South Asian	0.011%	9,108
Admixed American	0.01%	10,001
European (non-Finnish)	0.00483%	20,703
Finnishnot grpmax-eligible	0.00312%	32,011

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.Arg47Gln
Coding: c.140G>A
MANE Select: NM_001383
dbSNP: rs202050177
Type: single nucleotide variant
Location: chr17:2033583 (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.Arg47Trp Uncertain significance ★★ ⚠ same residue
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

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-arg47gln (accessed [today's date]).

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