Is ADSS1 p.Ala69= (c.207C>T) pathogenic?

ADSS1 p.Ala69= (c.207C>T) is classified Likely benign in ADSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). Ultra-rare (popmax 0.0362%, sas).

How common is ADSS1 p.Ala69= (c.207C>T) in the general population?

ADSS1 p.Ala69= (c.207C>T) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

ADSS1 p.Ala69=

c.207C>T · rs761935811 · VCV1681903

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, 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 -14	GERP -13
Overall
CADD	0.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% South Asian · 33/91,064 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.0036% 58/1,612,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
African / African-American	0.00934%	10,706
Finnishnot grpmax-eligible	0.00314%	31,894
East Asian	0.00223%	44,836
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.0011%	90,719

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.Ala69=
Coding: c.207C>T
MANE Select: NM_152328
dbSNP: rs761935811
Type: single nucleotide variant
Location: chr14:104735034 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.10
Residue 69: a binding site

Full ADSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADSS1 p.Ala69Thr Uncertain significance ★ ⚠ same residue
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

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-ala69 (accessed [today's date]).

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