Is ALAD p.Pro67Arg (c.200C>G) pathogenic?

ALAD p.Pro67Arg (c.200C>G) is classified Uncertain significance in ALAD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: ambiguous (0.3845); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALAD p.Pro67Arg (c.200C>G)?

ALAD p.Pro67Arg (c.200C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALAD p.Pro67Arg (c.200C>G) in the general population?

ALAD p.Pro67Arg (c.200C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALAD p.Pro67Arg (c.200C>G)?

AlphaMissense predicts ambiguous (score 0.3845) — an in-silico prediction, not a clinical call.

ALAD p.Pro67Arg

c.200C>G · VCV4036335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3845 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3845	ambiguous
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -13.52	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
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 0.72	unconstrained · MANE · 5,256 bp · p 6.2e-09 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALAD
Protein: p.Pro67Arg
Coding: c.200C>G
MANE Select: NM_000031
Type: single nucleotide variant
Location: chr9:113391588 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.10 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.34 · 4 PDB
Residue 67: an α-helix

Full ALAD 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

ALAD p.Arg17Gln Uncertain significance ★★ ⚠ same condition
ALAD p.Arg222Cys Uncertain significance ★★ ⚠ same condition
ALAD p.Arg90Gln Uncertain significance ★★ ⚠ same condition
ALAD p.Asp239Asn Uncertain significance ★★ ⚠ same condition
ALAD p.Gln45His Uncertain significance ★★ ⚠ same condition
ALAD p.Gly292Arg Uncertain significance ★★ ⚠ same condition
ALAD p.Met304Thr Uncertain significance ★★ ⚠ same condition
ALAD p.Ser197Arg 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/alad-p-pro67arg (accessed [today's date]).

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