Is DIABLO p.Ala3Val (c.8C>T) pathogenic?

DIABLO p.Ala3Val (c.8C>T) is classified Uncertain significance in DIABLO (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely benign (0.3263); Absent from gnomAD v4.1.

How common is DIABLO p.Ala3Val (c.8C>T) in the general population?

DIABLO p.Ala3Val (c.8C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIABLO p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely benign (score 0.3263) — an in-silico prediction, not a clinical call.

DIABLO p.Ala3Val

c.8C>T · rs202028496 · VCV2249532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3263 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,474)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3263	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 0.55, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 18 kb · p 0.08 · regional, not allelic
Overall
CADD	23.7	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

No allele count reported in gnomAD v4.1 (AN 1,603,474). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DIABLO
Protein: p.Ala3Val
Coding: c.8C>T
MANE Select: NM_001371333
dbSNP: rs202028496
Type: single nucleotide variant
Location: chr12:122226007 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.53 · 16 PDB

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

Similar variants

DIABLO p.Ala3Gly Likely benign ★★ ⚠ same residue
DIABLO p.Arg10Cys Uncertain significance ★★ ⚠ same type
DIABLO p.Ser9Leu Uncertain significance ★★ ⚠ same type
DIABLO p.Tyr117His Uncertain significance ★★ ⚠ same type
DIABLO c.183+63G>A Benign ★★ same type
DIABLO c.184-70G>A Benign ★★ same type
DIABLO c.316-101T>C Likely benign ★★ same type
DIABLO c.316-258A>T Benign ★★ 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/diablo-p-ala3val (accessed [today's date]).

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