Is ASS1 p.His167= (c.501C>T) pathogenic?

ASS1 p.His167= (c.501C>T) is classified Benign in ASS1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 12.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with citrullinemia.

What condition is associated with ASS1 p.His167= (c.501C>T)?

ASS1 p.His167= (c.501C>T) is associated with citrullinemia, citrullinemia type I (ClinVar).

ASS1 p.His167=

Q: How common is ASS1 p.His167= (c.501C>T) in the general population?

ASS1 p.His167= (c.501C>T) is common (popmax 12.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.501C>T · rs10901072 · VCV92369

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 12.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

citrullinemia

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 -12	GERP -2.2
Overall
CADD	0.319	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.5% European (non-Finnish) · 147,107/1,179,710 alleles

Filtering AF 12.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.4%

Overall 12.2% 197,122/1,613,678 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	19.3%	5
Amishnot grpmax-eligible	13.4%	7
European (non-Finnish)grpmax	12.5%	8
South Asian	12.1%	8
Remaining individualsnot grpmax-eligible	12%	8
Middle Eastern	11.9%	8
African / African-American	11.9%	8
Ashkenazi Jewishnot grpmax-eligible	11.8%	8
Admixed American	7.77%	13
East Asian	2.78%	36

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASS1
Protein: p.His167=
Coding: c.501C>T
MANE Select: NM_054012
dbSNP: rs10901072
Type: single nucleotide variant
Location: chr9:130470839 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 167: a UniProt-annotated variant site (in ctln1)

Full ASS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

citrullinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: citrullinemia type I

Similar variants

ASS1 p.His167Arg Uncertain significance ★ ⚠ same residue
ASS1 c.1194-1G>C Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.174+1G>T Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.175-1119G>A Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.364-2A>C Pathogenic/Likely pathogenic ★★ same condition
ASS1 c.364-2A>G Pathogenic ★★ same condition
ASS1 c.364-2A>T Likely pathogenic ★★ 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/ass1-p-his167 (accessed [today's date]).

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