Is FOXI3 p.Phe234Val (c.700T>G) pathogenic?

FOXI3 p.Phe234Val (c.700T>G) is classified Pathogenic/Likely pathogenic in FOXI3 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2023-07-13). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with craniofacial microsomia.

What condition is associated with FOXI3 p.Phe234Val (c.700T>G)?

FOXI3 p.Phe234Val (c.700T>G) is associated with craniofacial microsomia, craniofacial microsomia 2 (ClinVar).

How common is FOXI3 p.Phe234Val (c.700T>G) in the general population?

FOXI3 p.Phe234Val (c.700T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXI3 p.Phe234Val (c.700T>G)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

FOXI3 p.Phe234Val

c.700T>G · rs2528910500 · VCV2431349

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

craniofacial microsomia

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 6% in FOXI3
SaProt	LLR -15.11	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,722 bp · p 0.18 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

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: FOXI3
Protein: p.Phe234Val
Coding: c.700T>G
MANE Select: NM_001135649
dbSNP: rs2528910500
Type: single nucleotide variant
Location: chr2:88448770 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI 0.65 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.00
Residue 234: a DNA-binding region; a UniProt-annotated variant site (in cfm2; decreased transcription factor activity; does not affect localization to the nucleus); a UniProt-annotated variant site (in cfm2; decreased transcription factor activity; localization to the nucleus but aggregating into granular foci); the 'disordered' region

Full FOXI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

craniofacial microsomia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: craniofacial microsomia 2

Similar variants

FOXI3 p.Phe234Leu Uncertain significance ★ ⚠ same residue
FOXI3 p.Arg236Trp Likely pathogenic ★★ same condition
FOXI3 p.Arg238Ter Uncertain significance ★★ same condition
FOXI3 p.Leu199Arg Likely pathogenic ★ same condition
FOXI3 p.Phe234fs Likely pathogenic ★ same residue
FOXI3 p.Arg240Cys Uncertain significance ★ ⚠ same condition
FOXI3 p.Cys225Arg Likely pathogenic same condition
FOXI3 p.Phe102Tyr 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/foxi3-p-phe234val (accessed [today's date]).

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