Is ASS1 p.Phe72Ile (c.214T>A) pathogenic?

ASS1 p.Phe72Ile (c.214T>A) is classified Likely pathogenic in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-19). AlphaMissense: likely pathogenic (0.835); Very rare (popmax 0.00134%, afr); Associated with citrullinemia.

What condition is associated with ASS1 p.Phe72Ile (c.214T>A)?

ASS1 p.Phe72Ile (c.214T>A) is associated with citrullinemia (ClinVar).

How common is ASS1 p.Phe72Ile (c.214T>A) in the general population?

ASS1 p.Phe72Ile (c.214T>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ASS1 p.Phe72Ile (c.214T>A)?

AlphaMissense predicts likely pathogenic (score 0.835) — an in-silico prediction, not a clinical call.

ASS1 p.Phe72Ile

c.214T>A · rs1845500156 · VCV3012916

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

citrullinemia

Computational evidence

Protein change
AlphaMissense	0.835	likely pathogenic ✓ concordant with ClinVar
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -10.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	27.9	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

Grpmax group 0.00134% African / African-American · 1/74,822 alleles

Overall 0.000658% 1/152,018 alleles · very rare

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.Phe72Ile
Coding: c.214T>A
MANE Select: NM_054012
dbSNP: rs1845500156
Type: single nucleotide variant
Location: chr9:130458440 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 72: an α-helix; 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

Similar variants

ASS1 p.Phe72Leu Conflicting classifications of pathogenicity ★ ⚠ 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>T Likely pathogenic ★★ same condition
ASS1 c.421-2A>G Pathogenic ★★ same condition
ASS1 c.496-2A>G Pathogenic/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-phe72ile (accessed [today's date]).

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