Is C9 p.Phe306Ser (c.917T>C) pathogenic?

C9 p.Phe306Ser (c.917T>C) is classified Likely benign in C9 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9784); Absent from gnomAD v4.1; Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with C9 p.Phe306Ser (c.917T>C)?

C9 p.Phe306Ser (c.917T>C) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is C9 p.Phe306Ser (c.917T>C) in the general population?

C9 p.Phe306Ser (c.917T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C9 p.Phe306Ser (c.917T>C)?

AlphaMissense predicts likely pathogenic (score 0.9784) — an in-silico prediction, not a clinical call.

C9 p.Phe306Ser

c.917T>C · rs2479167375 · VCV2681688

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9784 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
AlphaMissense	0.9784	likely pathogenic · top 3% in C9
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -12.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 79 kb · p 0.0043 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C9
Protein: p.Phe306Ser
Coding: c.917T>C
MANE Select: NM_001737
dbSNP: rs2479167375
Type: single nucleotide variant
Location: chr5:39311331 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.32 · 9 PDB
Residue 306: the macpf domain; a β-strand

Full C9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

C9 c.871-2A>G Likely pathogenic ★★ same condition
C9 p.Arg116Ter Pathogenic/Likely pathogenic ★★ same condition
C9 p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
C9 p.Arg86Ter Pathogenic/Likely pathogenic ★★ same condition
C9 p.Cys54Ter Pathogenic/Likely pathogenic ★★ same condition
C9 c.1241-2A>G Likely pathogenic ★ same condition
C9 c.1240+2T>C Conflicting classifications of pathogenicity ★ same condition
C9 p.Thr109Lys Uncertain significance ★ ⚠ same condition

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/c9-p-phe306ser (accessed [today's date]).

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