Is AARD p.Pro32Leu (c.95C>T) pathogenic?

AARD p.Pro32Leu (c.95C>T) is classified Uncertain significance in AARD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1256); Very rare (popmax 0.000508%, nfe).

How common is AARD p.Pro32Leu (c.95C>T) in the general population?

AARD p.Pro32Leu (c.95C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about AARD p.Pro32Leu (c.95C>T)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

AARD p.Pro32Leu

c.95C>T · VCV4216564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.68	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 0.68	GERP 0.43
Regional constraint	o/e 1.12	unconstrained · MANE · 4,454 bp · p 0.076 · regional, not allelic
Overall
CADD	17.41	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 0.000508% European (non-Finnish) · 6/1,179,950 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,904 alleles · very rare

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: AARD
Protein: p.Pro32Leu
Coding: c.95C>T
MANE Select: NM_001025357
Type: single nucleotide variant
Location: chr8:116938338 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.24

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

Similar variants

AARD p.Ala70= Benign ★★ same type
AARD p.Ala82Thr Uncertain significance ★ ⚠ same type
AARD p.Ala82Val Uncertain significance ★ ⚠ same type
AARD p.Ala83Gly Uncertain significance ★ ⚠ same type
AARD p.Ala85Gly Uncertain significance ★ ⚠ same type
AARD p.Arg103Thr Uncertain significance ★ ⚠ same type
AARD p.Asp150Glu Uncertain significance ★ ⚠ same type
AARD p.Gln130Lys 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/aard-p-pro32leu (accessed [today's date]).

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