Is DPH5 p.Val17Leu (c.49G>C) pathogenic?

DPH5 p.Val17Leu (c.49G>C) is classified Uncertain significance in DPH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.2352); Absent from gnomAD v4.1.

How common is DPH5 p.Val17Leu (c.49G>C) in the general population?

DPH5 p.Val17Leu (c.49G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPH5 p.Val17Leu (c.49G>C)?

AlphaMissense predicts likely benign (score 0.2352) — an in-silico prediction, not a clinical call.

DPH5 p.Val17Leu

c.49G>C · VCV3842228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2352 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2352	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -8.46	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 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.15 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPH5
Protein: p.Val17Leu
Coding: c.49G>C
MANE Select: NM_015958
Type: single nucleotide variant
Location: chr1:101025395 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20

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-val17leu (accessed [today's date]).

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