Is DPH2 p.Arg201His (c.602G>A) pathogenic?

DPH2 p.Arg201His (c.602G>A) is classified Uncertain significance in DPH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2941); Very rare (popmax 0.00898%, nfe).

How common is DPH2 p.Arg201His (c.602G>A) in the general population?

DPH2 p.Arg201His (c.602G>A) is very rare (popmax 0.00898%, nfe) (gnomAD).

What do computational predictors say about DPH2 p.Arg201His (c.602G>A)?

AlphaMissense predicts likely benign (score 0.2941) — an in-silico prediction, not a clinical call.

DPH2 p.Arg201His

c.602G>A · rs148897061 · VCV2458123

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00898%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2941	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,712 bp · p 0.054 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00898% European (non-Finnish) · 106/1,180,042 alleles

Filtering AF 0.00757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00706%

Overall 0.00675% 109/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00898%	11,132
Remaining individualsnot grpmax-eligible	0.0032%	31,245
South Asian	0.0011%	91,092

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: DPH2
Protein: p.Arg201His
Coding: c.602G>A
MANE Select: NM_001384
dbSNP: rs148897061
Type: single nucleotide variant
Location: chr1:43971504 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60
Residue 201: a UniProt-annotated variant site (in dedssh2; severely impairs diphthamide modification of elongation factor 2)

Full DPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH2 p.Arg201Cys Uncertain significance ★ ⚠ same residue
DPH2 p.Arg477Ter Likely pathogenic ★ same type
DPH2 p.Ser75Ter Likely pathogenic ★ same type
DPH2 p.Ala310Val Uncertain significance ★ ⚠ same type
DPH2 p.Ala345Thr Uncertain significance ★ ⚠ same type
DPH2 p.Ala448Thr Uncertain significance ★ ⚠ same type
DPH2 p.Arg125His Uncertain significance ★ ⚠ same type
DPH2 p.Arg169Cys 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/dph2-p-arg201his (accessed [today's date]).

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