Is SERPINF1 p.Val5= (c.15G>T) pathogenic?

SERPINF1 p.Val5= (c.15G>T) is classified Conflicting classifications of pathogenicity in SERPINF1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-31). Rare (popmax 0.12%, sas); Associated with osteogenesis imperfecta.

What condition is associated with SERPINF1 p.Val5= (c.15G>T)?

SERPINF1 p.Val5= (c.15G>T) is associated with osteogenesis imperfecta, osteogenesis imperfecta type 6 (ClinVar).

How common is SERPINF1 p.Val5= (c.15G>T) in the general population?

SERPINF1 p.Val5= (c.15G>T) is rare (popmax 0.12%, sas) (gnomAD).

How is Osteogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SERPINF1 p.Val5=

c.15G>T · rs139841572 · VCV890646

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, sas)

Conditions

osteogenesis imperfecta

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 2.5	GERP 0.13, phastCons 0.98
Overall
CADD	2.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% South Asian · 102/84,790 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0927% 1,450/1,563,390 alleles · rare exomes 1,353/1,411,090 · genomes 97/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.12%	831
European (non-Finnish)	0.111%	903
Remaining individualsnot grpmax-eligible	0.0776%	1,288
Middle Eastern	0.0336%	2,979
Admixed American	0.0153%	6,555
African / African-American	0.0122%	8,202
Finnishnot grpmax-eligible	0.00663%	15,094
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,726

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: SERPINF1
Protein: p.Val5=
Coding: c.15G>T
MANE Select: NM_002615
dbSNP: rs139841572
Type: single nucleotide variant
Location: chr17:1766925 (GRCh38)
Gene constraint: LOEUF 1.06 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.86 · 3 PDB

Full SERPINF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: osteogenesis imperfecta type 6

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

SERPINF1 c.787-617G>A Likely pathogenic ★★ same condition
SERPINF1 p.Arg303Ter Pathogenic/Likely pathogenic ★★ same condition
SERPINF1 p.Arg99Ter Pathogenic ★★ same condition
SERPINF1 p.Gln178Ter Pathogenic ★★ same condition
SERPINF1 p.Gln185Ter Pathogenic ★★ same condition
SERPINF1 p.Gln2Ter Likely pathogenic ★★ same condition
SERPINF1 p.Gly270Ter Pathogenic ★★ same condition
SERPINF1 c.-37C>A Uncertain significance ★★ 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/serpinf1-p-val5 (accessed [today's date]).

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