IRF6 p.Phe375Ser
c.1124T>C · VCV4931282
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9995 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
IRF6-related condition
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9995 | likely pathogenic ✓ concordant with ClinVar · top 4% in IRF6 |
|---|---|---|
| REVEL | 0.95 | strongly pathogenic-leaning |
| SaProt | LLR -17.25 | 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 0.75, phastCons 1 |
| Regional constraint | o/e 0.56 | unconstrained · MANE · 3,658 bp · p 7.6e-11 · regional, not allelic |
| Overall | ||
| CADD | 27.8 | 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.Phe375Ser
- Coding
- c.1124T>C
- MANE Select
- NM_006147
- Type
- single nucleotide variant
- Location
- chr1:209789722 (GRCh38)
- Gene constraint
- LOEUF 0.214 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.19
Similar variants
- IRF6 p.Arg250Gln Pathogenic/Likely pathogenic ★★ same condition
- IRF6 p.Arg400Trp Pathogenic ★★ same condition
- IRF6 p.Arg412Ter Pathogenic ★★ same condition
- IRF6 p.Arg6Cys Pathogenic/Likely pathogenic ★★ same condition
- IRF6 p.Arg84Cys Pathogenic/Likely pathogenic ★★ same condition
- IRF6 p.Arg9Trp Pathogenic/Likely pathogenic ★★ same condition
- IRF6 p.Asn88Ser Pathogenic ★★ same condition
- IRF6 p.Gln152Ter Pathogenic/Likely pathogenic ★★ 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/irf6-p-phe375ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown