Is SF1 p.Pro74fs (c.221del) pathogenic?

SF1 p.Pro74fs (c.221del) is classified Likely pathogenic in SF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-04). No allele count reported in gnomAD v4.1 (AN 1,613,734); Associated with neurodevelopmental disorder.

What condition is associated with SF1 p.Pro74fs (c.221del)?

SF1 p.Pro74fs (c.221del) is associated with neurodevelopmental disorder (ClinVar).

How common is SF1 p.Pro74fs (c.221del) in the general population?

SF1 p.Pro74fs (c.221del) is no allele count reported in gnomAD v4.1 (AN 1,613,734) (gnomAD).

SF1 p.Pro74fs

c.221del · rs1430022410 · VCV1321942

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,734)

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,734). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SF1
Protein: p.Pro74fs
Coding: c.221del
MANE Select: NM_004630
dbSNP: rs1430022410
Type: Deletion
Location: chr11:64773445 (GRCh38)
Gene constraint: LOEUF 0.22 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.28 · 10 PDB
Residue 74: the 'disordered' region; an α-helix

Full SF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SF1 p.Ile53Arg Uncertain significance ★ ⚠ same condition
SF1 p.Pro590fs Likely pathogenic ★ same type
SF1 c.31+28del 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/sf1-p-pro74fs (accessed [today's date]).

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