Is ADO p.Pro144Leu (c.431C>T) pathogenic?

ADO p.Pro144Leu (c.431C>T) is classified Uncertain significance in ADO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.0976); Very rare (popmax 0.00396%, amr).

How common is ADO p.Pro144Leu (c.431C>T) in the general population?

ADO p.Pro144Leu (c.431C>T) is very rare (popmax 0.00396%, amr) (gnomAD).

What do computational predictors say about ADO p.Pro144Leu (c.431C>T)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

ADO p.Pro144Leu

c.431C>T · rs1265760800 · VCV3089965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00396%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -0.18, phastCons 0.83
Regional constraint	o/e 0.92	unconstrained · MANE · 809 bp · p 0.12 · regional, not allelic
Overall
CADD	17.73	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00396% Admixed American · 2/50,484 alleles

Filtering AF 0.000657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000246%

Overall 0.00039% 6/1,537,704 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00396%	25,242
African / African-American	0.00139%	71,798
European (non-Finnish)	0.000262%	381,716

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: ADO
Protein: p.Pro144Leu
Coding: c.431C>T
MANE Select: NM_032804
dbSNP: rs1265760800
Type: single nucleotide variant
Location: chr10:62805490 (GRCh38)
Gene constraint: LOEUF 1.476 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.28 · 9 PDB
Residue 144: the 'disordered' region

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

Similar variants

ADO p.Ala146Val Uncertain significance ★ ⚠ same type
ADO p.Ala14Ser Uncertain significance ★ ⚠ same type
ADO p.Ala41Val Uncertain significance ★ ⚠ same type
ADO p.Arg230Gly Uncertain significance ★ ⚠ same type
ADO p.Arg33Cys Uncertain significance ★ ⚠ same type
ADO p.Asp215Val Uncertain significance ★ ⚠ same type
ADO p.Asp219Glu Uncertain significance ★ ⚠ same type
ADO p.Asp34His Uncertain significance ★ ⚠ 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/ado-p-pro144leu (accessed [today's date]).

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