Is ALDOA p.Ser71Pro (c.211T>C) pathogenic?

ALDOA p.Ser71Pro (c.211T>C) is classified Uncertain significance in ALDOA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely pathogenic (0.9475); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALDOA p.Ser71Pro (c.211T>C)?

ALDOA p.Ser71Pro (c.211T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ALDOA p.Ser71Pro (c.211T>C) in the general population?

ALDOA p.Ser71Pro (c.211T>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about ALDOA p.Ser71Pro (c.211T>C)?

AlphaMissense predicts likely pathogenic (score 0.9475) — an in-silico prediction, not a clinical call.

ALDOA p.Ser71Pro

c.211T>C · VCV4037452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9475	likely pathogenic
REVEL	0.444	indeterminate
SaProt	LLR -15.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.1, phastCons 0.067
Regional constraint	o/e 0.91	unconstrained · MANE · 3,311 bp · p 0.028 · regional, not allelic
Overall
CADD	18.67	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S17P vs ClinVar S71P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,004 alleles

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

Overall 0.000411% 6/1,460,728 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: ALDOA
Protein: p.Ser71Pro
Coding: c.211T>C
MANE Select: NM_001243177
Type: single nucleotide variant
Location: chr16:30067303 (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 71: an α-helix

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.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
ALDOA p.Arg76His 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-ser71pro (accessed [today's date]).

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