Is AADAC p.Pro271Ala (c.811C>G) pathogenic?

AADAC p.Pro271Ala (c.811C>G) is classified Uncertain significance in AADAC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely benign (0.1243); Absent from gnomAD v4.1.

How common is AADAC p.Pro271Ala (c.811C>G) in the general population?

AADAC p.Pro271Ala (c.811C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AADAC p.Pro271Ala (c.811C>G)?

AlphaMissense predicts likely benign (score 0.1243) — an in-silico prediction, not a clinical call.

AADAC p.Pro271Ala

c.811C>G · VCV3785003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1243 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1243	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -9.75	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 0.78	GERP 1, phastCons 0.004
Regional constraint	o/e 0.98	unconstrained · MANE · 14 kb · p 0.68 · regional, not allelic
Overall
CADD	21.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AADAC
Protein: p.Pro271Ala
Coding: c.811C>G
MANE Select: NM_001086
Type: single nucleotide variant
Location: chr3:151827783 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64

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

Similar variants

AADAC p.Ala121Gly Uncertain significance ★ ⚠ same type
AADAC p.Ala16Val Uncertain significance ★ ⚠ same type
AADAC p.Ala319Glu Uncertain significance ★ ⚠ same type
AADAC p.Arg146Ser Uncertain significance ★ same type
AADAC p.Arg169Cys Uncertain significance ★ ⚠ same type
AADAC p.Arg169His Uncertain significance ★ ⚠ same type
AADAC p.Arg330Cys Uncertain significance ★ ⚠ same type
AADAC p.Arg92Gly 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/aadac-p-pro271ala (accessed [today's date]).

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