Is DPH7 p.Ala198Val (c.593C>T) pathogenic?

DPH7 p.Ala198Val (c.593C>T) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.4626); Absent from gnomAD v4.1.

How common is DPH7 p.Ala198Val (c.593C>T) in the general population?

DPH7 p.Ala198Val (c.593C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPH7 p.Ala198Val (c.593C>T)?

AlphaMissense predicts ambiguous (score 0.4626) — an in-silico prediction, not a clinical call.

DPH7 p.Ala198Val

c.593C>T · VCV4661949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4626 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4626	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -12.09	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	29.1	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

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: DPH7
Protein: p.Ala198Val
Coding: c.593C>T
MANE Select: NM_138778
Type: single nucleotide variant
Location: chr9:137574255 (GRCh38)
Gene constraint: LOEUF 1.37 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.62

Full DPH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH7 p.Ala198Pro Uncertain significance ★ ⚠ same residue
DPH7 p.Ala198Thr Uncertain significance ★ ⚠ same residue
DPH7 p.Ala105Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala16Thr Uncertain significance ★ same type
DPH7 p.Ala193Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala427Thr Uncertain significance ★ ⚠ same type
DPH7 p.Arg237Ser Uncertain significance ★ ⚠ same type
DPH7 p.Arg270Gln 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/dph7-p-ala198val (accessed [today's date]).

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