Is ADSS2 p.Ala390Val (c.1169C>T) pathogenic?

ADSS2 p.Ala390Val (c.1169C>T) is classified Uncertain significance in ADSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely pathogenic (0.687); Absent from gnomAD v4.1.

How common is ADSS2 p.Ala390Val (c.1169C>T) in the general population?

ADSS2 p.Ala390Val (c.1169C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADSS2 p.Ala390Val (c.1169C>T)?

AlphaMissense predicts likely pathogenic (score 0.687) — an in-silico prediction, not a clinical call.

ADSS2 p.Ala390Val

c.1169C>T · VCV4638677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.687	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 9,179 bp · p 0.0025 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADSS2
Protein: p.Ala390Val
Coding: c.1169C>T
MANE Select: NM_001126
Type: single nucleotide variant
Location: chr1:244411436 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 92.90 · 1 PDB

Full ADSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADSS2 p.Ala349Thr Uncertain significance ★ ⚠ same type
ADSS2 p.Ala417Ser Uncertain significance ★ ⚠ same type
ADSS2 p.Ala417Val Uncertain significance ★ ⚠ same type
ADSS2 p.Asn409Lys Uncertain significance ★ ⚠ same type
ADSS2 p.Asn90Lys Uncertain significance ★ ⚠ same type
ADSS2 p.Asp17Asn Uncertain significance ★ ⚠ same type
ADSS2 p.Asp381Asn Uncertain significance ★ ⚠ same type
ADSS2 p.Asp53Glu Uncertain significance ★ ⚠ 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/adss2-p-ala390val (accessed [today's date]).

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