Is DPH5 p.Phe270Ile (c.808T>A) pathogenic?

DPH5 p.Phe270Ile (c.808T>A) is classified Uncertain significance in DPH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: ambiguous (0.503); Very rare (popmax 8.47e-05%, nfe).

How common is DPH5 p.Phe270Ile (c.808T>A) in the general population?

DPH5 p.Phe270Ile (c.808T>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DPH5 p.Phe270Ile (c.808T>A)?

AlphaMissense predicts ambiguous (score 0.503) — an in-silico prediction, not a clinical call.

DPH5 p.Phe270Ile

c.808T>A · VCV4244424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.503 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.503	ambiguous
REVEL	0.344	indeterminate
SaProt	LLR -11.19	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.15 · regional, not allelic
Overall
CADD	23.4	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 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.2e-05% 1/1,614,148 alleles · very rare exomes 1/1,461,860 · genomes 0/152,288 · joint denominator

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.Phe270Ile
Coding: c.808T>A
MANE Select: NM_015958
Type: single nucleotide variant
Location: chr1:100990458 (GRCh38)

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

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-phe270ile (accessed [today's date]).

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