Is ASS1 p.Ala202Val (c.605C>T) pathogenic?

ASS1 p.Ala202Val (c.605C>T) is classified Uncertain significance in ASS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-03-16). AlphaMissense: ambiguous (0.4274); Very rare (popmax 0.00223%, eas).

How common is ASS1 p.Ala202Val (c.605C>T) in the general population?

ASS1 p.Ala202Val (c.605C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ASS1 p.Ala202Val (c.605C>T)?

AlphaMissense predicts ambiguous (score 0.4274) — an in-silico prediction, not a clinical call.

ASS1 p.Ala202Val

c.605C>T · VCV3353737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4274 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4274	ambiguous
REVEL	0.571	indeterminate
SaProt	LLR -4.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	23.5	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 0.00223% East Asian · 1/44,886 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,613,856 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
European (non-Finnish)	0.00186%	53,634
African / African-American	0.00134%	74,902
South Asian	0.0011%	91,080

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.Ala202Val
Coding: c.605C>T
MANE Select: NM_054012
Type: single nucleotide variant
Location: chr9:130476878 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 202: an α-helix; a UniProt-annotated variant site (in ctln1)

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

Similar variants

ASS1 p.Ala202Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
ASS1 p.Ala202= Likely benign ★ same residue
ASS1 c.1194-1G>C Pathogenic/Likely pathogenic ★★ same type
ASS1 c.174+1G>A Pathogenic/Likely pathogenic ★★ same type
ASS1 c.174+1G>T Pathogenic/Likely pathogenic ★★ same type
ASS1 c.175-1119G>A Pathogenic/Likely pathogenic ★★ same type
ASS1 c.364-2A>C Pathogenic/Likely pathogenic ★★ same type
ASS1 c.364-2A>G Pathogenic ★★ same type

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-ala202val (accessed [today's date]).

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