Is FLI1 p.Asp33= (c.99C>T) pathogenic?

FLI1 p.Asp33= (c.99C>T) is classified Likely benign in FLI1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00364%, nfe).

How common is FLI1 p.Asp33= (c.99C>T) in the general population?

FLI1 p.Asp33= (c.99C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

FLI1 p.Asp33=

c.99C>T · rs754201848 · VCV2874005

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

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 2.1	GERP 0.85, phastCons 1
Overall
CADD	11.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,179,738 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00273% 44/1,613,404 alleles · very rare exomes 42/1,461,232 · genomes 2/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,436
Remaining individualsnot grpmax-eligible	0.0016%	62,444

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.Asp33=
Coding: c.99C>T
MANE Select: NM_002017
dbSNP: rs754201848
Type: single nucleotide variant
Location: chr11:128758195 (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

Similar variants

FLI1 p.Asp33Asn Uncertain significance ★ ⚠ same residue
FLI1 p.Ala178Thr Uncertain significance ★★ ⚠ same type
FLI1 p.Ala247Thr Uncertain significance ★★ ⚠ same type
FLI1 p.Ala295Ser Uncertain significance ★★ ⚠ same type
FLI1 p.Ala419Thr Uncertain significance ★★ ⚠ same type
FLI1 p.Arg177His Uncertain significance ★★ ⚠ same type
FLI1 p.Arg177Pro Uncertain significance ★★ ⚠ same type
FLI1 p.Arg257Gln Uncertain significance ★★ ⚠ 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/fli1-p-asp33 (accessed [today's date]).

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