Is IRF6 p.Pro24Ser (c.70C>T) pathogenic?

IRF6 p.Pro24Ser (c.70C>T) is classified Likely benign in IRF6 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.5849); Absent from gnomAD v4.1; Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with IRF6 p.Pro24Ser (c.70C>T)?

IRF6 p.Pro24Ser (c.70C>T) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is IRF6 p.Pro24Ser (c.70C>T) in the general population?

IRF6 p.Pro24Ser (c.70C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IRF6 p.Pro24Ser (c.70C>T)?

AlphaMissense predicts likely pathogenic (score 0.5849) — an in-silico prediction, not a clinical call.

IRF6 p.Pro24Ser

c.70C>T · rs2464694692 · VCV2681336

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5849 · 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	0.5849	likely pathogenic
REVEL	0.734	pathogenic-leaning
SaProt	LLR -11.22	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 4,991 bp · p 1.5e-12 · regional, not allelic
Overall
CADD	29.8	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: IRF6
Protein: p.Pro24Ser
Coding: c.70C>T
MANE Select: NM_006147
dbSNP: rs2464694692
Type: single nucleotide variant
Location: chr1:209801344 (GRCh38)
Gene constraint: LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 24: a DNA-binding region

Full IRF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

IRF6 p.Pro24Leu Likely pathogenic ★ same residue
IRF6 c.1060+1G>A Pathogenic/Likely pathogenic ★★ same type
IRF6 p.Arg250Gln Pathogenic/Likely pathogenic ★★ same type
IRF6 p.Arg250Ter Pathogenic ★★ same type
IRF6 p.Arg400Trp Pathogenic ★★ same type
IRF6 p.Arg412Ter Pathogenic ★★ same type
IRF6 p.Arg6Cys Pathogenic/Likely pathogenic ★★ same type
IRF6 p.Arg84Cys Pathogenic/Likely pathogenic ★★ 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/irf6-p-pro24ser (accessed [today's date]).

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