Is DPH1 p.Pro244Arg (c.731C>G) pathogenic?

DPH1 p.Pro244Arg (c.731C>G) is classified Benign/Likely benign in DPH1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.223); Rare (popmax 0.726%, mid).

How common is DPH1 p.Pro244Arg (c.731C>G) in the general population?

DPH1 p.Pro244Arg (c.731C>G) is rare (popmax 0.726%, mid) (gnomAD).

What do computational predictors say about DPH1 p.Pro244Arg (c.731C>G)?

AlphaMissense predicts likely benign (score 0.223) — an in-silico prediction, not a clinical call.

DPH1 p.Pro244Arg

c.731C>G · rs80150196 · VCV791430

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.223 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.726%, mid)

Computational evidence

Protein change
AlphaMissense	0.223	likely benign
REVEL	0.508	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.074 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P249R vs ClinVar P244R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.726% Middle Eastern · 44/6,062 alleles

Filtering AF 0.625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.607%

Overall 0.508% 8,207/1,614,154 alleles · rare exomes 7,646/1,461,822 · genomes 561/152,332 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.726%	138
South Asian	0.669%	150
European (non-Finnish)	0.571%	175
Remaining individualsnot grpmax-eligible	0.467%	214
Finnishnot grpmax-eligible	0.388%	258
Admixed American	0.31%	323
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
African / African-American	0.0799%	1,251

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.Pro244Arg
Coding: c.731C>G
MANE Select: NM_001383
dbSNP: rs80150196
Type: single nucleotide variant
Location: chr17:2039805 (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

Similar variants

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
DPH1 p.Arg47Trp Uncertain significance ★★ ⚠ same type
DPH1 p.Asp231Glu Uncertain significance ★★ ⚠ same type
DPH1 p.Gln269His Uncertain significance ★★ ⚠ same type
DPH1 p.Ile241Phe 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-pro244arg (accessed [today's date]).

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