Is ADA p.Arg101Trp (c.301C>T) pathogenic?

ADA p.Arg101Trp (c.301C>T) is classified Pathogenic/Likely pathogenic in ADA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-09-16). AlphaMissense: likely pathogenic (0.8145); Very rare (popmax 0.00331%, nfe); Associated with ADA-related disorder.

How common is ADA p.Arg101Trp (c.301C>T) in the general population?

ADA p.Arg101Trp (c.301C>T) is very rare (popmax 0.00331%, nfe) (gnomAD).

What do computational predictors say about ADA p.Arg101Trp (c.301C>T)?

AlphaMissense predicts likely pathogenic (score 0.8145) — an in-silico prediction, not a clinical call.

ADA p.Arg101Trp

Q: What condition is associated with ADA p.Arg101Trp (c.301C>T)?

ADA p.Arg101Trp (c.301C>T) is associated with ADA-related disorder, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (ClinVar).

c.301C>T · rs121908717 · VCV1955

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8145 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ADA-related disorder

Computational evidence

Protein change
AlphaMissense	0.8145	likely pathogenic ✓ concordant with ClinVar
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -15.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.21 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00331% European (non-Finnish) · 39/1,180,024 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00254% 41/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,257
South Asian	0.0022%	45,540

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: ADA
Protein: p.Arg101Trp
Coding: c.301C>T
MANE Select: NM_000022
dbSNP: rs121908717
Type: single nucleotide variant
Location: chr20:44626517 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 101: a UniProt-annotated variant site (in adascid); a UniProt-annotated variant site (in adascid; loss of activity); a β-strand

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

Disease context

ADA-related disorder

Also linked: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Similar variants

ADA p.Arg101Gln Pathogenic ★★ same residue
ADA p.Arg101Leu Pathogenic/Likely pathogenic ★★ same residue
ADA p.Arg101Gly Likely pathogenic ★ same residue
ADA p.Arg101= Likely benign ★ same residue
ADA c.1078+2T>A Likely pathogenic ★★★ same condition
ADA c.219-2A>G Likely pathogenic ★★★ same condition
ADA c.363-2A>G Likely pathogenic ★★★ same condition
ADA c.606+1G>T Likely 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-arg101trp (accessed [today's date]).

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