Is ADA p.Arg156Ser (c.466C>A) pathogenic?

ADA p.Arg156Ser (c.466C>A) is classified Likely pathogenic in ADA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely pathogenic (0.9411); No allele count reported in gnomAD v4.1 (AN 1,582,160); Associated with severe combined immunodeficiency.

What condition is associated with ADA p.Arg156Ser (c.466C>A)?

ADA p.Arg156Ser (c.466C>A) is associated with severe combined immunodeficiency (ClinVar).

How common is ADA p.Arg156Ser (c.466C>A) in the general population?

ADA p.Arg156Ser (c.466C>A) is no allele count reported in gnomAD v4.1 (AN 1,582,160) (gnomAD).

What do computational predictors say about ADA p.Arg156Ser (c.466C>A)?

AlphaMissense predicts likely pathogenic (score 0.9411) — an in-silico prediction, not a clinical call.

ADA p.Arg156Ser

c.466C>A · rs121908735 · VCV3251901

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9411 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,160)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

severe combined immunodeficiency

Computational evidence

Protein change
AlphaMissense	0.9411	likely pathogenic ✓ concordant with ClinVar · top 10% in ADA
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -11.72	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 9.8	GERP 0.16, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.21 · regional, not allelic
Overall
CADD	31.0	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

No allele count reported in gnomAD v4.1 (AN 1,582,160). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADA
Protein: p.Arg156Ser
Coding: c.466C>A
MANE Select: NM_000022
dbSNP: rs121908735
Type: single nucleotide variant
Location: chr20:44625581 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 156: a UniProt-annotated variant site (in adascid); a UniProt-annotated variant site (in adascid; loss of activity)

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

Disease context

severe combined immunodeficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADA p.Arg156Cys Pathogenic ★★ same residue
ADA p.Arg156His Pathogenic/Likely pathogenic ★★ same residue
ADA p.Arg156Leu Pathogenic ★ same residue
ADA p.Arg156Pro Likely pathogenic ★ same residue
ADA c.975+1G>A Pathogenic ★★★ same condition
ADA p.Arg211Cys Likely pathogenic ★★★ ⚠ same condition
ADA p.Arg282Gln Pathogenic ★★★ ⚠ same condition
ADA p.Gly239Asp Pathogenic ★★★ same condition

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-arg156ser (accessed [today's date]).

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