Is DPH2 p.Ser391Phe (c.1172C>T) pathogenic?

DPH2 p.Ser391Phe (c.1172C>T) is classified Uncertain significance in DPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: ambiguous (0.3433); Very rare (popmax 0.00254%, nfe).

How common is DPH2 p.Ser391Phe (c.1172C>T) in the general population?

DPH2 p.Ser391Phe (c.1172C>T) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about DPH2 p.Ser391Phe (c.1172C>T)?

AlphaMissense predicts ambiguous (score 0.3433) — an in-silico prediction, not a clinical call.

DPH2 p.Ser391Phe

c.1172C>T · VCV3504875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3433 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3433	ambiguous
REVEL	0.15	moderately benign-leaning
SaProt	LLR -12.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 603 bp · p 0.64 · regional, not allelic
Overall
CADD	26.1	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 0.00254% European (non-Finnish) · 30/1,179,574 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00212% 31/1,461,134 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,319
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Ser391Phe
Coding: c.1172C>T
MANE Select: NM_001384
Type: single nucleotide variant
Location: chr1:43972161 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60
Residue 391: 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.Arg201His Uncertain significance ★★ ⚠ same type
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-ser391phe (accessed [today's date]).

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