Is LFNG p.Arg360Cys (c.1078C>T) pathogenic?

LFNG p.Arg360Cys (c.1078C>T) is classified Uncertain significance in LFNG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-18). AlphaMissense: ambiguous (0.4804); Ultra-rare (popmax 0.0123%, nfe); Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Arg360Cys (c.1078C>T)?

LFNG p.Arg360Cys (c.1078C>T) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.Arg360Cys (c.1078C>T) in the general population?

LFNG p.Arg360Cys (c.1078C>T) is ultra-rare (popmax 0.0123%, nfe) (gnomAD).

What do computational predictors say about LFNG p.Arg360Cys (c.1078C>T)?

AlphaMissense predicts ambiguous (score 0.4804) — an in-silico prediction, not a clinical call.

LFNG p.Arg360Cys

c.1078C>T · rs763938391 · VCV1418979

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4804 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, nfe)

Conditions

spondylocostal dysostosis 3, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.4804	ambiguous
REVEL	0.324	indeterminate
SaProt	LLR -11.03	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.42, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,453 bp · p 0.44 · regional, not allelic
Overall
CADD	33.0	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 0.0123% European (non-Finnish) · 145/1,179,892 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00997%

Overall 0.00986% 159/1,612,546 alleles · ultra-rare exomes 140/1,460,420 · genomes 19/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0123%	8,137
Finnishnot grpmax-eligible	0.00956%	10,457
Remaining individualsnot grpmax-eligible	0.00801%	12,492
Admixed American	0.00333%	29,998
East Asian	0.00223%	44,878

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: LFNG
Protein: p.Arg360Cys
Coding: c.1078C>T
MANE Select: NM_001040167
dbSNP: rs763938391
Type: single nucleotide variant
Location: chr7:2527150 (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-arg360cys (accessed [today's date]).

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