Is DPH2 p.Arg201Cys (c.601C>T) pathogenic?

DPH2 p.Arg201Cys (c.601C>T) is classified Uncertain significance in DPH2 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-06-04). AlphaMissense: likely benign (0.2837); Very rare (popmax 0.0033%, nfe); Associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2.

How common is DPH2 p.Arg201Cys (c.601C>T) in the general population?

DPH2 p.Arg201Cys (c.601C>T) is very rare (popmax 0.0033%, nfe) (gnomAD).

What do computational predictors say about DPH2 p.Arg201Cys (c.601C>T)?

AlphaMissense predicts likely benign (score 0.2837) — an in-silico prediction, not a clinical call.

DPH2 p.Arg201Cys

Q: What condition is associated with DPH2 p.Arg201Cys (c.601C>T)?

DPH2 p.Arg201Cys (c.601C>T) is associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2 (ClinVar).

c.601C>T · rs767455462 · VCV872919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Computational evidence

Protein change
AlphaMissense	0.2837	likely benign
REVEL	0.376	indeterminate
SaProt	LLR -13.16	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,712 bp · p 0.054 · regional, not allelic
Overall
CADD	25.7	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 0.0033% European (non-Finnish) · 39/1,180,034 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00248% 40/1,614,094 alleles · very rare exomes 37/1,461,886 · genomes 3/152,208 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0033%	30,257
Admixed American	0.00167%	60,010

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.Arg201Cys
Coding: c.601C>T
MANE Select: NM_001384
dbSNP: rs767455462
Type: single nucleotide variant
Location: chr1:43971503 (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

Disease context

developmental delay with short stature, dysmorphic facial features, and sparse hair 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH2 p.Arg201His Uncertain significance ★★ ⚠ same residue
DPH2 p.Arg477Ter Likely pathogenic ★ same condition
DPH2 p.Ser75Ter Likely pathogenic ★ same condition
DPH2 p.Gln308Ter Uncertain significance ★ same condition
DPH2 p.Arg282fs Conflicting classifications of pathogenicity ★ same condition
DPH2 p.Ala310Val Uncertain significance ★ ⚠ same type
DPH2 p.Ala345Thr Uncertain significance ★ ⚠ same type
DPH2 p.Ala448Thr 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-arg201cys (accessed [today's date]).

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