Is CLDN9 p.Thr4= (c.12C>T) pathogenic?

CLDN9 p.Thr4= (c.12C>T) is classified Likely benign in CLDN9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). Ultra-rare (popmax 0.011%, sas).

How common is CLDN9 p.Thr4= (c.12C>T) in the general population?

CLDN9 p.Thr4= (c.12C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

CLDN9 p.Thr4=

c.12C>T · rs747724516 · VCV3067290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, 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 -5.2	GERP -3.7
Overall
CADD	0.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,026 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.0108% 174/1,611,322 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.161%	620
Remaining individualsnot grpmax-eligible	0.0192%	5,201
South Asiangrpmax	0.011%	9,103
European (non-Finnish)	0.00407%	24,563
Admixed American	0.00334%	29,970
African / African-American	0.00133%	74,920

Finnish 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: CLDN9
Protein: p.Thr4=
Coding: c.12C>T
MANE Select: NM_020982
dbSNP: rs747724516
Type: single nucleotide variant
Location: chr16:3013374 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.95 · 2 PDB

Full CLDN9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDN9 p.Arg205His Uncertain significance ★★ ⚠ same type
CLDN9 p.Ala170= Benign/Likely benign ★★ same type
CLDN9 p.Thr184= Likely benign ★★ same type
CLDN9 p.Arg116Cys Likely pathogenic ★ ⚠ same type
CLDN9 p.Ala115Thr Uncertain significance ★ ⚠ same type
CLDN9 p.Ala121Val Uncertain significance ★ ⚠ same type
CLDN9 p.Ala128Gly Uncertain significance ★ ⚠ same type
CLDN9 p.Ala128Thr 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/cldn9-p-thr4 (accessed [today's date]).

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