Is ADA p.Asp19Val (c.56A>T) pathogenic?

ADA p.Asp19Val (c.56A>T) is classified Likely pathogenic in ADA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.976); Absent from gnomAD v4.1.

How common is ADA p.Asp19Val (c.56A>T) in the general population?

ADA p.Asp19Val (c.56A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADA p.Asp19Val (c.56A>T)?

AlphaMissense predicts likely pathogenic (score 0.976) — an in-silico prediction, not a clinical call.

ADA p.Asp19Val

c.56A>T · rs2516197070 · VCV2571135

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.976	likely pathogenic ✓ concordant with ClinVar · top 4% in ADA
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -12.99	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 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.21 · regional, not allelic
Overall
CADD	27.8	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: ADA
Protein: p.Asp19Val
Coding: c.56A>T
MANE Select: NM_000022
dbSNP: rs2516197070
Type: single nucleotide variant
Location: chr20:44636266 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 19: a binding site; an α-helix

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

Similar variants

ADA p.Asp19Glu Uncertain significance ★ ⚠ same residue
ADA p.Asp19= Likely benign ★ same residue
ADA c.1078+2T>A Likely pathogenic ★★★ same type
ADA c.219-2A>G Likely pathogenic ★★★ same type
ADA c.363-2A>G Likely pathogenic ★★★ same type
ADA c.606+1G>T Likely pathogenic ★★★ same type
ADA c.975+1G>A Pathogenic ★★★ same type
ADA c.976-1G>C Pathogenic ★★★ 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/ada-p-asp19val (accessed [today's date]).

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