Is DPH7 p.Ala193Val (c.578C>T) pathogenic?

DPH7 p.Ala193Val (c.578C>T) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.6382); Ultra-rare (popmax 0.0841%, afr).

How common is DPH7 p.Ala193Val (c.578C>T) in the general population?

DPH7 p.Ala193Val (c.578C>T) is ultra-rare (popmax 0.0841%, afr) (gnomAD).

What do computational predictors say about DPH7 p.Ala193Val (c.578C>T)?

AlphaMissense predicts likely pathogenic (score 0.6382) — an in-silico prediction, not a clinical call.

DPH7 p.Ala193Val

c.578C>T · rs138535655 · VCV2457912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0841%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6382	likely pathogenic
REVEL	0.23	benign-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Constraint at this position
Conservation	phyloP 8.3	GERP 1.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	29.6	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 0.0841% African / African-American · 63/74,924 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00434% 70/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0841%	1,189
Admixed American	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0048%	20,828

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: DPH7
Protein: p.Ala193Val
Coding: c.578C>T
MANE Select: NM_138778
dbSNP: rs138535655
Type: single nucleotide variant
Location: chr9:137574270 (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.Ala105Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala16Thr Uncertain significance ★ same type
DPH7 p.Ala198Pro Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Val 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-ala193val (accessed [today's date]).

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