Is ALDOC p.Pro295Ser (c.883C>T) pathogenic?

ALDOC p.Pro295Ser (c.883C>T) is classified Uncertain significance in ALDOC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely pathogenic (0.867); Very rare (popmax 0.00667%, amr).

How common is ALDOC p.Pro295Ser (c.883C>T) in the general population?

ALDOC p.Pro295Ser (c.883C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ALDOC p.Pro295Ser (c.883C>T)?

AlphaMissense predicts likely pathogenic (score 0.867) — an in-silico prediction, not a clinical call.

ALDOC p.Pro295Ser

c.883C>T · VCV3520266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.867	likely pathogenic
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -13.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,003 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	28.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,012 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000558% 9/1,614,134 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,003
African / African-American	0.00267%	37,471
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000169%	590,023

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: ALDOC
Protein: p.Pro295Ser
Coding: c.883C>T
MANE Select: NM_005165
Type: single nucleotide variant
Location: chr17:28573851 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 1 PDB
Residue 295: a β-strand

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

Similar variants

ALDOC p.Pro295Leu Uncertain significance ★ ⚠ same residue
ALDOC p.Ala136Asp Uncertain significance ★ ⚠ same type
ALDOC p.Ala297Thr Uncertain significance ★ ⚠ same type
ALDOC p.Ala297Val Uncertain significance ★ ⚠ same type
ALDOC p.Ala32Ser Uncertain significance ★ ⚠ same type
ALDOC p.Arg134Cys Uncertain significance ★ ⚠ same type
ALDOC p.Arg134His Uncertain significance ★ ⚠ same type
ALDOC p.Arg149Cys 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/aldoc-p-pro295ser (accessed [today's date]).

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