Is DPH7 p.Glu82Ala (c.245A>C) pathogenic?

DPH7 p.Glu82Ala (c.245A>C) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: ambiguous (0.4654); Very rare (popmax 0.000274%).

How common is DPH7 p.Glu82Ala (c.245A>C) in the general population?

DPH7 p.Glu82Ala (c.245A>C) is very rare (popmax 0.000274%) (gnomAD).

What do computational predictors say about DPH7 p.Glu82Ala (c.245A>C)?

AlphaMissense predicts ambiguous (score 0.4654) — an in-silico prediction, not a clinical call.

DPH7 p.Glu82Ala

c.245A>C · rs1390256264 · VCV2604815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000274%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4654	ambiguous
REVEL	0.22	benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.39, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	26.0	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 0.000274%

Overall 0.000274% 4/1,461,768 alleles · very rare

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.Glu82Ala
Coding: c.245A>C
MANE Select: NM_138778
dbSNP: rs1390256264
Type: single nucleotide variant
Location: chr9:137577512 (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.Ala193Val 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

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-glu82ala (accessed [today's date]).

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