Is FLI1 p.Val12= (c.36G>A) pathogenic?

FLI1 p.Val12= (c.36G>A) is classified Likely benign in FLI1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-06). Very rare (popmax 0.00223%, eas); Associated with FLI1-related disorder.

What condition is associated with FLI1 p.Val12= (c.36G>A)?

FLI1 p.Val12= (c.36G>A) is associated with FLI1-related disorder (ClinVar).

How common is FLI1 p.Val12= (c.36G>A) in the general population?

FLI1 p.Val12= (c.36G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

FLI1 p.Val12=

c.36G>A · rs1241457903 · VCV3029389

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

FLI1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -1.3, phastCons 1
Overall
CADD	11.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,838 alleles

Overall 0.000248% 4/1,612,712 alleles · very rare exomes 3/1,460,470 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,558
East Asiangrpmax	0.00223%	44,838
Remaining individualsnot grpmax-eligible	0.0016%	62,414
European (non-Finnish)	8.48e-05%	1,179,432

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FLI1
Protein: p.Val12=
Coding: c.36G>A
MANE Select: NM_002017
dbSNP: rs1241457903
Type: single nucleotide variant
Location: chr11:128758132 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 14 PDB

Full FLI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FLI1-related disorder

Similar variants

FLI1 p.Arg340His Conflicting classifications of pathogenicity ★ ⚠ same condition
FLI1 p.Glu375Lys Uncertain significance ★ ⚠ same condition
FLI1 p.Asn275= Likely benign same condition
FLI1 p.Glu96= Likely benign same condition
FLI1 p.Ile300= Likely benign same condition
FLI1 p.Ala338fs Likely pathogenic ★ same condition
FLI1 p.Lys354fs Likely pathogenic ★ same condition
FLI1 p.Pro113fs 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/fli1-p-val12 (accessed [today's date]).

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