Is AIDA p.Ser147Ala (c.439T>G) pathogenic?

AIDA p.Ser147Ala (c.439T>G) is classified Uncertain significance in AIDA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0527); Very rare (popmax 0.00017%, nfe).

How common is AIDA p.Ser147Ala (c.439T>G) in the general population?

AIDA p.Ser147Ala (c.439T>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about AIDA p.Ser147Ala (c.439T>G)?

AlphaMissense predicts likely benign (score 0.0527) — an in-silico prediction, not a clinical call.

AIDA p.Ser147Ala

c.439T>G · VCV4639433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0527	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.50	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 6	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 0.028 · regional, not allelic
Overall
CADD	19.33	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 0.00017% European (non-Finnish) · 2/1,179,940 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,506 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: AIDA
Protein: p.Ser147Ala
Coding: c.439T>G
MANE Select: NM_022831
Type: single nucleotide variant
Location: chr1:222686951 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.37
Residue 147: the 'disordered' region

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

Similar variants

AIDA p.Asn51Ser Uncertain significance ★ ⚠ same type
AIDA p.Asp134Tyr Uncertain significance ★ ⚠ same type
AIDA p.Asp186Asn Uncertain significance ★ ⚠ same type
AIDA p.Cys69Arg Uncertain significance ★ ⚠ same type
AIDA p.Glu265Val Uncertain significance ★ ⚠ same type
AIDA p.Glu45Lys Uncertain significance ★ ⚠ same type
AIDA p.Gly198Ser Uncertain significance ★ ⚠ same type
AIDA p.Gly236Asp 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/aida-p-ser147ala (accessed [today's date]).

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