Is ALAD p.Ser5= (c.15C>T) pathogenic?

ALAD p.Ser5= (c.15C>T) is classified Benign/Likely benign in ALAD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-31). Rare (popmax 0.664%, afr); Associated with porphyria due to ALA dehydratase deficiency.

What condition is associated with ALAD p.Ser5= (c.15C>T)?

ALAD p.Ser5= (c.15C>T) is associated with porphyria due to ALA dehydratase deficiency (ClinVar).

How common is ALAD p.Ser5= (c.15C>T) in the general population?

ALAD p.Ser5= (c.15C>T) is rare (popmax 0.664%, afr) (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.Ser5=

c.15C>T · rs144608303 · VCV364656

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.664%, afr)

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 -4.8	GERP -4
Overall
CADD	1.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.664% African / African-American · 498/75,046 alleles

Filtering AF 0.615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.596%

Overall 0.036% 581/1,613,558 alleles · rare exomes 304/1,461,216 · genomes 277/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.664%	151
Remaining individualsnot grpmax-eligible	0.0593%	1,688
Admixed American	0.035%	2,858
East Asian	0.0245%	4,081
Middle Eastern	0.018%	5,558
South Asian	0.00439%	22,762
European (non-Finnish)	0.000763%	131,111

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.Ser5=
Coding: c.15C>T
MANE Select: NM_000031
dbSNP: rs144608303
Type: single nucleotide variant
Location: chr9:113393545 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.10 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.34 · 4 PDB

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-ser5 (accessed [today's date]).

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