Is LFNG p.Ser44Ile (c.131G>T) pathogenic?

LFNG p.Ser44Ile (c.131G>T) is classified Uncertain significance in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-30). AlphaMissense: ambiguous (0.5546); Absent from gnomAD v4.1; Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Ser44Ile (c.131G>T)?

LFNG p.Ser44Ile (c.131G>T) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.Ser44Ile (c.131G>T) in the general population?

LFNG p.Ser44Ile (c.131G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LFNG p.Ser44Ile (c.131G>T)?

AlphaMissense predicts ambiguous (score 0.5546) — an in-silico prediction, not a clinical call.

LFNG p.Ser44Ile

c.131G>T · rs1369297768 · VCV1045090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5546 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

spondylocostal dysostosis 3, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.5546	ambiguous
REVEL	0.164	moderately benign-leaning
SaProt	LLR -9.32	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 5,828 bp · p 0.78 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LFNG
Protein: p.Ser44Ile
Coding: c.131G>T
MANE Select: NM_001040167
dbSNP: rs1369297768
Type: single nucleotide variant
Location: chr7:2519992 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.66

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

Disease context

spondylocostal dysostosis 3, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LFNG p.Thr145Met Likely pathogenic ★★ same condition
LFNG c.482-3C>T Uncertain significance ★★ same condition
LFNG p.Ala95Val Uncertain significance ★★ ⚠ same condition
LFNG p.Ala99Thr Uncertain significance ★★ ⚠ same condition
LFNG p.Arg187Cys Uncertain significance ★★ ⚠ same condition
LFNG p.Arg239Trp Uncertain significance ★★ ⚠ same condition
LFNG p.Arg246His Uncertain significance ★★ ⚠ same condition
LFNG p.Arg341Gln 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/lfng-p-ser44ile (accessed [today's date]).

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