Is ADSS1 p.Val331Ala (c.992T>C) pathogenic?

ADSS1 p.Val331Ala (c.992T>C) is classified Uncertain significance in ADSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely pathogenic (0.7876); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with ADSS1 p.Val331Ala (c.992T>C)?

ADSS1 p.Val331Ala (c.992T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ADSS1 p.Val331Ala (c.992T>C) in the general population?

ADSS1 p.Val331Ala (c.992T>C) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ADSS1 p.Val331Ala (c.992T>C)?

AlphaMissense predicts likely pathogenic (score 0.7876) — an in-silico prediction, not a clinical call.

ADSS1 p.Val331Ala

c.992T>C · rs759971233 · VCV3091220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7876	likely pathogenic
REVEL	0.403	indeterminate
SaProt	LLR -6.47	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 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 23 kb · p 0.77 · regional, not allelic
Overall
CADD	27.3	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 0.00439% South Asian · 4/91,068 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000411% 6/1,460,838 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,767
European (non-Finnish)	0.000169%	589,981

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: ADSS1
Protein: p.Val331Ala
Coding: c.992T>C
MANE Select: NM_152328
dbSNP: rs759971233
Type: single nucleotide variant
Location: chr14:104743110 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.10
Residue 331: a binding site

Full ADSS1 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

ADSS1 c.193-4823C>A Uncertain significance ★★ same condition
ADSS1 c.193-4836G>A Uncertain significance ★★ same condition
ADSS1 c.193-4838G>A Uncertain significance ★★ same condition
ADSS1 c.193-4866C>T Uncertain significance ★★ same condition
ADSS1 c.193-4916C>T Uncertain significance ★★ same condition
ADSS1 c.193-4956C>A Uncertain significance ★★ same condition
ADSS1 c.193-5075G>A Uncertain significance ★★ same condition
ADSS1 c.193-5091C>G 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/adss1-p-val331ala (accessed [today's date]).

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