Is CCR9 p.Ile92Val (c.274A>G) pathogenic?

CCR9 p.Ile92Val (c.274A>G) is classified Benign in CCR9 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0593); Low-frequency (popmax 1.08%, nfe).

How common is CCR9 p.Ile92Val (c.274A>G) in the general population?

CCR9 p.Ile92Val (c.274A>G) is low-frequency (popmax 1.08%, nfe) (gnomAD).

What do computational predictors say about CCR9 p.Ile92Val (c.274A>G)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

CCR9 p.Ile92Val

c.274A>G · VCV3770410

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.82	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 1.1	GERP -1, phastCons 0.02
Overall
CADD	11.83	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% European (non-Finnish) · 12,686/1,180,026 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.887% 14,316/1,614,156 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.08%	93
Remaining individualsnot grpmax-eligible	1.01%	99
Finnishnot grpmax-eligible	0.734%	136
Middle Eastern	0.379%	264
Admixed American	0.237%	423
South Asian	0.222%	451
African / African-American	0.18%	556
Ashkenazi Jewishnot grpmax-eligible	0.098%	1,021

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.Ile92Val
Coding: c.274A>G
MANE Select: NM_001296 · reported on NM_031200
Type: single nucleotide variant
Location: chr3:45901062 (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-ile92val (accessed [today's date]).

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