Is CTR9 p.Thr498= (c.1494C>T) pathogenic?

CTR9 p.Thr498= (c.1494C>T) is classified Benign in CTR9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 30.9%, nfe) — too common for a highly-penetrant pathogenic allele.

CTR9 p.Thr498=

Q: How common is CTR9 p.Thr498= (c.1494C>T) in the general population?

CTR9 p.Thr498= (c.1494C>T) is common (popmax 30.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1494C>T · rs7118399 · VCV1165251

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 30.9%, nfe) — too common for a highly-penetrant pathogenic allele

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 0.27	GERP -4.1, phastCons 0.72
Overall
CADD	1.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.9% European (non-Finnish) · 364,774/1,178,810 alleles

Filtering AF 30.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.8%

Overall 28.4% 458,223/1,612,318 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	37.8%	3
Finnishnot grpmax-eligible	31.1%	3
European (non-Finnish)grpmax	30.9%	3
Remaining individualsnot grpmax-eligible	27.7%	4
Middle Eastern	26.7%	4
Ashkenazi Jewishnot grpmax-eligible	25.1%	4
South Asian	20.5%	5
Admixed American	18.2%	5
East Asian	15.9%	6
African / African-American	13.6%	7

Amish 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: CTR9
Protein: p.Thr498=
Coding: c.1494C>T
MANE Select: NM_014633
dbSNP: rs7118399
Type: single nucleotide variant
Location: chr11:10764628 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 498: an α-helix

Full CTR9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTR9 p.Thr498Ser Uncertain significance ★★ ⚠ same residue
CTR9 p.Asn455Ser Likely pathogenic ★★ same type
CTR9 p.Ile17Thr Pathogenic/Likely pathogenic ★★ same type
CTR9 p.Pro25Arg Pathogenic/Likely pathogenic ★★ same type
CTR9 c.1960+3G>A Uncertain significance ★★ same type
CTR9 c.2109+4A>G Uncertain significance ★★ same type
CTR9 c.2445-3T>C Uncertain significance ★★ same type
CTR9 c.45+5G>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/ctr9-p-thr498 (accessed [today's date]).

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