Is ADSS1 p.Ser193Phe (c.578C>T) pathogenic?

ADSS1 p.Ser193Phe (c.578C>T) is classified Uncertain significance in ADSS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-02). AlphaMissense: likely benign (0.3023); Rare (popmax 0.135%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADSS1 p.Ser193Phe (c.578C>T)?

ADSS1 p.Ser193Phe (c.578C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADSS1 p.Ser193Phe (c.578C>T) in the general population?

ADSS1 p.Ser193Phe (c.578C>T) is rare (popmax 0.135%, nfe) (gnomAD).

What do computational predictors say about ADSS1 p.Ser193Phe (c.578C>T)?

AlphaMissense predicts likely benign (score 0.3023) — an in-silico prediction, not a clinical call.

ADSS1 p.Ser193Phe

c.578C>T · rs144784529 · VCV2070421

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3023 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3023	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -14.43	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 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 23 kb · p 0.77 · regional, not allelic
Overall
CADD	26.7	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 0.135% European (non-Finnish) · 1,590/1,179,998 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.104% 1,680/1,613,832 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.135%	742
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Finnishnot grpmax-eligible	0.0235%	4,261
African / African-American	0.0227%	4,405
Admixed American	0.02%	5,000
East Asian	0.00668%	14,961
South Asian	0.0011%	91,076

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.Ser193Phe
Coding: c.578C>T
MANE Select: NM_152328
dbSNP: rs144784529
Type: single nucleotide variant
Location: chr14:104740702 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.10

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 p.Ser193= Benign ★★ same residue
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

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-ser193phe (accessed [today's date]).

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