Is FLI1 p.Ser79Pro (c.235T>C) pathogenic?

FLI1 p.Ser79Pro (c.235T>C) is classified Uncertain significance in FLI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely pathogenic (0.6561); Very rare (popmax 0.00335%, amr).

How common is FLI1 p.Ser79Pro (c.235T>C) in the general population?

FLI1 p.Ser79Pro (c.235T>C) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about FLI1 p.Ser79Pro (c.235T>C)?

AlphaMissense predicts likely pathogenic (score 0.6561) — an in-silico prediction, not a clinical call.

FLI1 p.Ser79Pro

c.235T>C · rs1266575591 · VCV2184233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6561	likely pathogenic
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 74 kb · p 0.014 · regional, not allelic
Overall
CADD	24.8	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

Grpmax group 0.00335% Admixed American · 2/59,636 alleles

Filtering AF 0.000556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000248% 4/1,610,280 alleles · very rare exomes 3/1,458,546 · genomes 1/151,734 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,818
South Asian	0.0011%	90,660
European (non-Finnish)	8.49e-05%	1,177,849

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.Ser79Pro
Coding: c.235T>C
MANE Select: NM_002017
dbSNP: rs1266575591
Type: single nucleotide variant
Location: chr11:128768122 (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.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
FLI1 p.Asn435Ser 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-ser79pro (accessed [today's date]).

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