Is DPH5 p.Pro273Thr (c.817C>A) pathogenic?

DPH5 p.Pro273Thr (c.817C>A) is classified Uncertain significance in DPH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-06). AlphaMissense: likely benign (0.06); Very rare (popmax 0.00161%, nfe).

How common is DPH5 p.Pro273Thr (c.817C>A) in the general population?

DPH5 p.Pro273Thr (c.817C>A) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about DPH5 p.Pro273Thr (c.817C>A)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

DPH5 p.Pro273Thr

c.817C>A · rs749204630 · VCV3085490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.06	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -0.52, phastCons 0.59
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.15 · regional, not allelic
Overall
CADD	11.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,956 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00137% 20/1,461,834 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,103
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: DPH5
Protein: p.Pro273Thr
Coding: c.817C>A
MANE Select: NM_015958
dbSNP: rs749204630
Type: single nucleotide variant
Location: chr1:100990449 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20
Residue 273: a UniProt-annotated variant site (in nedsff; loss of function in diphthamide biosynthesis shown in a yeast assay system)

Full DPH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH5 p.His260Arg Pathogenic/Likely pathogenic ★★ same type
DPH5 p.Pro104Thr Uncertain significance ★★ ⚠ same type
DPH5 c.260+1G>T Likely pathogenic ★ same type
DPH5 p.Ala111Ser Uncertain significance ★ ⚠ same type
DPH5 p.Ala223Val Uncertain significance ★ ⚠ same type
DPH5 p.Ala234Pro Uncertain significance ★ ⚠ same type
DPH5 p.Ala33Ser Uncertain significance ★ ⚠ same type
DPH5 p.Arg224Ser 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/dph5-p-pro273thr (accessed [today's date]).

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