Is ADA p.Asp345Glu (c.1035C>G) pathogenic?

ADA p.Asp345Glu (c.1035C>G) is classified Likely benign in ADA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-25). AlphaMissense: likely benign (0.1431); Absent from gnomAD v4.1.

How common is ADA p.Asp345Glu (c.1035C>G) in the general population?

ADA p.Asp345Glu (c.1035C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADA p.Asp345Glu (c.1035C>G)?

AlphaMissense predicts likely benign (score 0.1431) — an in-silico prediction, not a clinical call.

ADA p.Asp345Glu

c.1035C>G · VCV4945118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1431 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1431	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -6.34	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 -3.5	GERP -2.8
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.21 · regional, not allelic
Overall
CADD	0.046	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.Asp345Glu
Coding: c.1035C>G
MANE Select: NM_000022
Type: single nucleotide variant
Location: chr20:44620342 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 345: an α-helix

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

Similar variants

ADA p.Asp345Tyr Uncertain significance ★ ⚠ same residue
ADA p.Asp345= 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-asp345glu (accessed [today's date]).

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