Is AADAC p.Val93Glu (c.278T>A) pathogenic?

AADAC p.Val93Glu (c.278T>A) is classified Uncertain significance in AADAC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.5795); Very rare (popmax 0.00119%, nfe).

How common is AADAC p.Val93Glu (c.278T>A) in the general population?

AADAC p.Val93Glu (c.278T>A) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about AADAC p.Val93Glu (c.278T>A)?

AlphaMissense predicts likely pathogenic (score 0.5795) — an in-silico prediction, not a clinical call.

AADAC p.Val93Glu

c.278T>A · VCV4635677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5795	likely pathogenic
REVEL	0.289	benign-leaning
SaProt	LLR -9.79	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 0.95	GERP 1.9, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.68 · regional, not allelic
Overall
CADD	24.3	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 0.00119% European (non-Finnish) · 14/1,179,754 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,640 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: AADAC
Protein: p.Val93Glu
Coding: c.278T>A
MANE Select: NM_001086
Type: single nucleotide variant
Location: chr3:151817505 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64

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

Similar variants

AADAC p.Ala121Gly Uncertain significance ★ ⚠ same type
AADAC p.Ala16Val Uncertain significance ★ ⚠ same type
AADAC p.Ala319Glu Uncertain significance ★ ⚠ same type
AADAC p.Arg146Ser Uncertain significance ★ ⚠ same type
AADAC p.Arg169Cys Uncertain significance ★ ⚠ same type
AADAC p.Arg169His Uncertain significance ★ ⚠ same type
AADAC p.Arg330Cys Uncertain significance ★ ⚠ same type
AADAC p.Arg92Gly 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/aadac-p-val93glu (accessed [today's date]).

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