Is CLDN9 p.Ala170= (c.510G>A) pathogenic?

CLDN9 p.Ala170= (c.510G>A) is classified Benign/Likely benign in CLDN9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Very rare (popmax 0.00935%, afr).

How common is CLDN9 p.Ala170= (c.510G>A) in the general population?

CLDN9 p.Ala170= (c.510G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

CLDN9 p.Ala170=

c.510G>A · VCV3911142

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

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 -20	GERP -3.7
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,870 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00378% 61/1,611,812 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,696
Remaining individualsnot grpmax-eligible	0.00641%	15,604
European (non-Finnish)	0.00407%	24,576
South Asian	0.0022%	45,521

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.Ala170=
Coding: c.510G>A
MANE Select: NM_020982
Type: single nucleotide variant
Location: chr16:3013872 (GRCh38)
Gene constraint: LOEUF 1.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.95 · 2 PDB
Residue 170: an α-helix

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.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
CLDN9 p.Ala140Val 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-ala170 (accessed [today's date]).

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