Is ADA p.Ser150Pro (c.448T>C) pathogenic?

ADA p.Ser150Pro (c.448T>C) is classified Uncertain significance in ADA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely pathogenic (0.8976); Absent from gnomAD v4.1.

How common is ADA p.Ser150Pro (c.448T>C) in the general population?

ADA p.Ser150Pro (c.448T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADA p.Ser150Pro (c.448T>C)?

AlphaMissense predicts likely pathogenic (score 0.8976) — an in-silico prediction, not a clinical call.

ADA p.Ser150Pro

c.448T>C · VCV4945125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8976 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,748)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8976	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -15.45	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 7.9	GERP -0.85, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.21 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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 1,588,748). 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.Ser150Pro
Coding: c.448T>C
MANE Select: NM_000022
Type: single nucleotide variant
Location: chr20:44625599 (GRCh38)
Gene constraint: LOEUF 1.184 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 150: a β-strand

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

Similar variants

ADA p.Ser150fs Pathogenic ★ 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
ADA p.Ala329Val 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-ser150pro (accessed [today's date]).

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