Is CCR9 p.Val259Ile (c.775G>A) pathogenic?

CCR9 p.Val259Ile (c.775G>A) is classified Uncertain significance in CCR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.1064); Very rare (popmax 0.000932%, nfe).

How common is CCR9 p.Val259Ile (c.775G>A) in the general population?

CCR9 p.Val259Ile (c.775G>A) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about CCR9 p.Val259Ile (c.775G>A)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

CCR9 p.Val259Ile

c.775G>A · VCV3264649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.6, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,046 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,614,082 alleles · very rare

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: CCR9
Protein: p.Val259Ile
Coding: c.775G>A
MANE Select: NM_001296 · reported on NM_031200
Type: single nucleotide variant
Location: chr3:45901563 (GRCh38)
Structure: AlphaFold pLDDT 80.89 · 3 PDB

Full CCR9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCR10 p.Leu267Met Uncertain significance ★★ ⚠ same type
CCR10 p.Pro155= Benign ★★ same type
CCR9 p.Leu136= Benign ★★ same type
ACKR2 p.Ala248Thr Uncertain significance ★ ⚠ same type
ACKR2 p.Cys284Arg Uncertain significance ★ same type
ACKR2 p.His317Tyr Uncertain significance ★ ⚠ same type
ACKR2 p.Ile56Val Uncertain significance ★ ⚠ same type
ACKR2 p.Leu59Trp 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/ccr9-p-val259ile (accessed [today's date]).

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