Is DAD1 p.Val8Ala (c.23T>C) pathogenic?

DAD1 p.Val8Ala (c.23T>C) is classified Uncertain significance in DAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely pathogenic (0.5859); Absent from gnomAD v4.1.

How common is DAD1 p.Val8Ala (c.23T>C) in the general population?

DAD1 p.Val8Ala (c.23T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAD1 p.Val8Ala (c.23T>C)?

AlphaMissense predicts likely pathogenic (score 0.5859) — an in-silico prediction, not a clinical call.

DAD1 p.Val8Ala

c.23T>C · rs2502947959 · VCV2275873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5859 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5859	likely pathogenic
REVEL	0.275	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 14 kb · p 0.12 · regional, not allelic
Overall
CADD	22.0	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

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: DAD1
Protein: p.Val8Ala
Coding: c.23T>C
MANE Select: NM_001344
dbSNP: rs2502947959
Type: single nucleotide variant
Location: chr14:22589135 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 6 PDB
Residue 8: an α-helix

Full DAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAD1 c.212-128T>C Benign ★★ same type
DAD1 c.*44+172T>C Benign ★★ same type
DAD1 c.*44+72A>T Benign ★★ same type
DAD1 p.Ter114= Benign ★★ same type
DAD1 p.Ala93Asp Uncertain significance ★ ⚠ same type
DAD1 p.Ala93Gly Uncertain significance ★ ⚠ same type
DAD1 p.Asn54Lys Uncertain significance ★ ⚠ same type
DAD1 p.Cys45Arg 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/dad1-p-val8ala (accessed [today's date]).

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