Is ASS1 p.Ala136Val (c.407C>T) pathogenic?

ASS1 p.Ala136Val (c.407C>T) is classified Uncertain significance in ASS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1306); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ASS1 p.Ala136Val (c.407C>T)?

ASS1 p.Ala136Val (c.407C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ASS1 p.Ala136Val (c.407C>T) in the general population?

ASS1 p.Ala136Val (c.407C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ASS1 p.Ala136Val (c.407C>T)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

ASS1 p.Ala136Val

c.407C>T · VCV4587094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 49 kb · p 6.7e-05 · regional, not allelic
Overall
CADD	21.3	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 0.00267% African / African-American · 2/74,928 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000867% 14/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,464
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000932%	107,272

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.Ala136Val
Coding: c.407C>T
MANE Select: NM_054012
Type: single nucleotide variant
Location: chr9:130464154 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 1 PDB
Residue 136: a UniProt-annotated variant site (in ctln1)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ASS1 p.Ala136= Likely benign ★ same residue
ASS1 p.Ala136Asp Uncertain significance ⚠ same residue
ASS1 p.Arg153Gln Uncertain significance ★★ ⚠ same condition
ASS1 p.Gly5Ala Uncertain significance ★★ ⚠ same condition
ASS1 p.Pro178Leu Uncertain significance ★★ ⚠ same condition
ASS1 p.Pro385Ala Uncertain significance ★★ ⚠ same condition
ASS1 p.Thr219Asn Uncertain significance ★★ ⚠ same condition
ASS1 p.Val379Met 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/ass1-p-ala136val (accessed [today's date]).

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