Is ADSS1 p.Pro268= (c.804C>T) pathogenic?

ADSS1 p.Pro268= (c.804C>T) is classified Likely benign in ADSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-21). Very rare (popmax 0.00988%, sas).

How common is ADSS1 p.Pro268= (c.804C>T) in the general population?

ADSS1 p.Pro268= (c.804C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

ADSS1 p.Pro268=

c.804C>T · rs767443349 · VCV1681970

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3.8
Overall
CADD	4.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,090 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000616% 9/1,460,982 alleles · very rare

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.Pro268=
Coding: c.804C>T
MANE Select: NM_152328
dbSNP: rs767443349
Type: single nucleotide variant
Location: chr14:104741858 (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

Similar variants

ADSS1 c.949-2A>G Likely pathogenic ★★ same type
ADSS1 p.Asp261Asn Pathogenic/Likely pathogenic ★★ same type
ADSS1 p.Gln323Ter Pathogenic/Likely pathogenic ★★ same type
ADSS1 c.193-4823C>A Uncertain significance ★★ same type
ADSS1 c.193-4836G>A Uncertain significance ★★ same type
ADSS1 c.193-4838G>A Uncertain significance ★★ same type
ADSS1 c.193-4866C>T Uncertain significance ★★ same type
ADSS1 c.193-4916C>T 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/adss1-p-pro268 (accessed [today's date]).

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