Is FOXRED1 p.Glu306Gln (c.916G>C) pathogenic?

FOXRED1 p.Glu306Gln (c.916G>C) is classified Uncertain significance in FOXRED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0864); Very rare (popmax 0.00223%, eas).

How common is FOXRED1 p.Glu306Gln (c.916G>C) in the general population?

FOXRED1 p.Glu306Gln (c.916G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about FOXRED1 p.Glu306Gln (c.916G>C)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

FOXRED1 p.Glu306Gln

c.916G>C · VCV4882673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -4.58	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 2	GERP -1.5, phastCons 0.65
Regional constraint	o/e 0.94	unconstrained · MANE · 8,479 bp · p 0.15 · regional, not allelic
Overall
CADD	5.855	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,752 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,611,018 alleles · very rare exomes 6/1,458,938 · genomes 0/152,080 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,752
European (non-Finnish)	0.000424%	235,870

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: FOXRED1
Protein: p.Glu306Gln
Coding: c.916G>C
MANE Select: NM_017547
Type: single nucleotide variant
Location: chr11:126276164 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.12
Residue 306: a UniProt-annotated variant site (in mc1dn19)

Full FOXRED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FOXRED1 c.733+1G>A Pathogenic/Likely pathogenic ★★ same type
FOXRED1 c.86-1G>A Pathogenic/Likely pathogenic ★★ same type
FOXRED1 p.Arg352Trp Pathogenic ★★ ⚠ same type
FOXRED1 p.Arg89Ter Likely pathogenic ★★ same type
FOXRED1 p.Cys331Ter Pathogenic/Likely pathogenic ★★ same type
FOXRED1 p.Gln232Ter Pathogenic ★★ same type
FOXRED1 p.Gln368Ter Pathogenic/Likely pathogenic ★★ same type
FOXRED1 p.Glu353Ter 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/foxred1-p-glu306gln (accessed [today's date]).

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