Is ALDOA p.Pro345Ser (c.1033C>T) pathogenic?

ALDOA p.Pro345Ser (c.1033C>T) is classified Uncertain significance in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely benign (0.1102); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with ALDOA p.Pro345Ser (c.1033C>T)?

ALDOA p.Pro345Ser (c.1033C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALDOA p.Pro345Ser (c.1033C>T) in the general population?

ALDOA p.Pro345Ser (c.1033C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about ALDOA p.Pro345Ser (c.1033C>T)?

AlphaMissense predicts likely benign (score 0.1102) — an in-silico prediction, not a clinical call.

ALDOA p.Pro345Ser

c.1033C>T · rs1283651383 · VCV2287697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1102	likely benign
REVEL	0.392	indeterminate
SaProt	LLR -12.66	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P291S vs ClinVar P345S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,094 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000558% 9/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,219
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.000169%	590,016

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: ALDOA
Protein: p.Pro345Ser
Coding: c.1033C>T
MANE Select: NM_001243177
dbSNP: rs1283651383
Type: single nucleotide variant
Location: chr16:30069901 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.53 · 8 PDB
Residue 345: a UniProt-annotated variant site (in gsd12)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALDOA p.Pro345Thr Uncertain significance ★ ⚠ same residue
ALDOA p.Ala217Thr Uncertain significance ★★ same condition
ALDOA p.Arg97Gln Uncertain significance ★★ same condition
ALDOA p.Arg97Pro Uncertain significance ★★ ⚠ same condition
ALDOA p.Asn339Ser Uncertain significance ★★ same condition
ALDOA p.Gly157Ser Uncertain significance ★★ ⚠ same condition
ALDOA p.Thr309Ile Uncertain significance ★★ ⚠ same condition
ALDOA p.Ala293Gly Uncertain significance ★ ⚠ same condition

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/aldoa-p-pro345ser (accessed [today's date]).

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