Is ALAD p.Gln290= (c.870G>A) pathogenic?

ALAD p.Gln290= (c.870G>A) is classified Uncertain significance in ALAD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0802%, eas); Associated with porphyria due to ALA dehydratase deficiency.

What condition is associated with ALAD p.Gln290= (c.870G>A)?

ALAD p.Gln290= (c.870G>A) is associated with porphyria due to ALA dehydratase deficiency (ClinVar).

How common is ALAD p.Gln290= (c.870G>A) in the general population?

ALAD p.Gln290= (c.870G>A) is ultra-rare (popmax 0.0802%, eas) (gnomAD).

How is Porphyria due to ALA dehydratase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALAD p.Gln290=

c.870G>A · rs759917153 · VCV913818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, eas)

Conditions

porphyria due to ALA dehydratase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.15, phastCons 1
Overall
CADD	5.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0802% East Asian · 36/44,902 alleles

Filtering AF 0.0594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00229% 37/1,613,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0802%	1,247
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: ALAD
Protein: p.Gln290=
Coding: c.870G>A
MANE Select: NM_000031
dbSNP: rs759917153
Type: single nucleotide variant
Location: chr9:113389038 (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 290: an α-helix

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

Disease context

porphyria due to ALA dehydratase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Porphyria due to ALA dehydratase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

ALAD p.Gly133Arg Likely pathogenic ★★ same condition
ALAD c.*127C>T Uncertain significance ★★ same condition
ALAD c.*363G>A Uncertain significance ★★ same condition
ALAD p.Ala93Thr Uncertain significance ★★ ⚠ same condition
ALAD p.Arg147Cys Uncertain significance ★★ ⚠ same condition
ALAD p.Arg174His Uncertain significance ★★ ⚠ same condition
ALAD p.Arg262Trp Uncertain significance ★★ ⚠ same condition
ALAD p.Asp239Asn 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-gln290 (accessed [today's date]).

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