Is ALDOC p.Cys202Arg (c.604T>C) pathogenic?

ALDOC p.Cys202Arg (c.604T>C) is classified Uncertain significance in ALDOC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.9915); Ultra-rare (popmax 0.0626%, sas).

How common is ALDOC p.Cys202Arg (c.604T>C) in the general population?

ALDOC p.Cys202Arg (c.604T>C) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

What do computational predictors say about ALDOC p.Cys202Arg (c.604T>C)?

AlphaMissense predicts likely pathogenic (score 0.9915) — an in-silico prediction, not a clinical call.

ALDOC p.Cys202Arg

c.604T>C · VCV4269831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9915 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9915	likely pathogenic
REVEL	0.846	moderately pathogenic-leaning
SaProt	LLR -17.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	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	28.3	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 0.0626% South Asian · 57/91,080 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00415% 67/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0048%	20,830
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)	0.000339%	295,000

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.Cys202Arg
Coding: c.604T>C
MANE Select: NM_005165
Type: single nucleotide variant
Location: chr17:28574514 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 1 PDB
Residue 202: an α-helix

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

Similar variants

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
ALDOC p.Arg157Cys 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-cys202arg (accessed [today's date]).

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