Is DAD1 p.Ala93Asp (c.278C>A) pathogenic?

DAD1 p.Ala93Asp (c.278C>A) is classified Uncertain significance in DAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely pathogenic (0.9917); Very rare (popmax 0.00229%, nfe).

How common is DAD1 p.Ala93Asp (c.278C>A) in the general population?

DAD1 p.Ala93Asp (c.278C>A) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about DAD1 p.Ala93Asp (c.278C>A)?

AlphaMissense predicts likely pathogenic (score 0.9917) — an in-silico prediction, not a clinical call.

DAD1 p.Ala93Asp

c.278C>A · VCV3838185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9917	likely pathogenic · top 8% in DAD1
REVEL	0.726	pathogenic-leaning
SaProt	LLR -14.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 14 kb · p 0.12 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,018 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00167% 27/1,614,156 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: DAD1
Protein: p.Ala93Asp
Coding: c.278C>A
MANE Select: NM_001344
Type: single nucleotide variant
Location: chr14:22575167 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 6 PDB
Residue 93: an α-helix

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

Similar variants

DAD1 p.Ala93Gly Uncertain significance ★ ⚠ same residue
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.Asn54Lys Uncertain significance ★ ⚠ same type
DAD1 p.Cys45Arg Uncertain significance ★ ⚠ same type
DAD1 p.Gln22Arg 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-ala93asp (accessed [today's date]).

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