Is CCR9 p.Phe114Ile (c.340T>A) pathogenic?

CCR9 p.Phe114Ile (c.340T>A) is classified Uncertain significance in CCR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.7288); Very rare (popmax 0.004%, afr).

How common is CCR9 p.Phe114Ile (c.340T>A) in the general population?

CCR9 p.Phe114Ile (c.340T>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CCR9 p.Phe114Ile (c.340T>A)?

AlphaMissense predicts likely pathogenic (score 0.7288) — an in-silico prediction, not a clinical call.

CCR9 p.Phe114Ile

c.340T>A · VCV4222297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7288	likely pathogenic · top 7% in CCR9
REVEL	0.568	indeterminate
SaProt	LLR -11.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2.6, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.004% African / African-American · 3/75,034 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000205% 3/1,461,876 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.Phe114Ile
Coding: c.340T>A
MANE Select: NM_001296 · reported on NM_031200
Type: single nucleotide variant
Location: chr3:45901128 (GRCh38)
Structure: AlphaFold pLDDT 80.89 · 3 PDB

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

Similar variants

CCR9 p.Phe114Leu Uncertain significance ★ ⚠ same residue
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

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-phe114ile (accessed [today's date]).

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