Is LIFR p.Pro11= (c.33A>G) pathogenic?

LIFR p.Pro11= (c.33A>G) is classified Likely benign in LIFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-23). Very rare (popmax 0.0011%, sas); Associated with Stüve-Wiedemann syndrome 1.

What condition is associated with LIFR p.Pro11= (c.33A>G)?

LIFR p.Pro11= (c.33A>G) is associated with Stüve-Wiedemann syndrome 1 (ClinVar).

How common is LIFR p.Pro11= (c.33A>G) in the general population?

LIFR p.Pro11= (c.33A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Schwartz-Jampel syndrome inherited?

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

LIFR p.Pro11=

c.33A>G · rs754559989 · VCV1989500

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Stüve-Wiedemann syndrome 1

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 -4	GERP -4
Overall
CADD	0.417	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,610 alleles · very rare exomes 6/1,461,280 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	0.000424%	235,905

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: LIFR
Protein: p.Pro11=
Coding: c.33A>G
MANE Select: NM_001127671
dbSNP: rs754559989
Type: single nucleotide variant
Location: chr5:38530615 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.10 · 6 PDB

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

Disease context

Stüve-Wiedemann syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Schwartz-Jampel syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

LIFR c.1121+1G>A Likely pathogenic ★★ same condition
LIFR c.1291+2T>C Likely pathogenic ★★ same condition
LIFR c.2497+1G>A Pathogenic/Likely pathogenic ★★ same condition
LIFR p.Ala622Val Likely pathogenic ★★ ⚠ same condition
LIFR p.Arg418Ter Pathogenic/Likely pathogenic ★★ same condition
LIFR p.Arg692Ter Pathogenic/Likely pathogenic ★★ same condition
LIFR p.Arg812Ter Pathogenic ★★ same condition
LIFR p.Glu109Ter 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/lifr-p-pro11 (accessed [today's date]).

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