Is CST9 p.Asn59= (c.177C>T) pathogenic?

CST9 p.Asn59= (c.177C>T) is classified Likely benign in CST9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Ultra-rare (popmax 0.0495%, mid).

How common is CST9 p.Asn59= (c.177C>T) in the general population?

CST9 p.Asn59= (c.177C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

CST9 p.Asn59=

c.177C>T · rs139668286 · VCV2652240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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 0.73	GERP -0.65, phastCons 0.44
Overall
CADD	6.308	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.0275% 444/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,346
Middle Easterngrpmax	0.0495%	2,021
Finnishnot grpmax-eligible	0.0437%	2,287
European (non-Finnish)	0.0316%	3,164
Remaining individualsnot grpmax-eligible	0.0096%	10,418
South Asian	0.00878%	11,383
Admixed American	0.005%	20,003
African / African-American	0.00133%	75,058

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CST9
Protein: p.Asn59=
Coding: c.177C>T
MANE Select: NM_001008693
dbSNP: rs139668286
Type: single nucleotide variant
Location: chr20:23605688 (GRCh38)
Gene constraint: LOEUF 1.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.21

Full CST9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST9 p.Ala13Ser Uncertain significance ★ ⚠ same type
CST9 p.Ala9Thr Uncertain significance ★ ⚠ same type
CST9 p.Arg78Ser Uncertain significance ★ ⚠ same type
CST9 p.Arg7Lys Uncertain significance ★ ⚠ same type
CST9 p.Arg99Cys Uncertain significance ★ ⚠ same type
CST9 p.Arg99His Uncertain significance ★ ⚠ same type
CST9 p.Asn123Asp Uncertain significance ★ ⚠ same type
CST9 p.Asn123Ser 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/cst9-p-asn59 (accessed [today's date]).

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