Is ALDOC p.Ala136Asp (c.407C>A) pathogenic?

ALDOC p.Ala136Asp (c.407C>A) is classified Uncertain significance in ALDOC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely pathogenic (0.6318); Very rare (popmax 0.00627%, nfe).

How common is ALDOC p.Ala136Asp (c.407C>A) in the general population?

ALDOC p.Ala136Asp (c.407C>A) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about ALDOC p.Ala136Asp (c.407C>A)?

AlphaMissense predicts likely pathogenic (score 0.6318) — an in-silico prediction, not a clinical call.

ALDOC p.Ala136Asp

c.407C>A · rs371220607 · VCV3110358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6318	likely pathogenic
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -14.33	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	31.0	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 0.00627% European (non-Finnish) · 74/1,180,044 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00465% 75/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,947
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Ala136Asp
Coding: c.407C>A
MANE Select: NM_005165
dbSNP: rs371220607
Type: single nucleotide variant
Location: chr17:28574829 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 1 PDB
Residue 136: an α-helix

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

Similar variants

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
ALDOC p.Arg157Cys Uncertain significance ★ ⚠ same type
ALDOC p.Arg173Cys 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-ala136asp (accessed [today's date]).

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