Is LFNG p.Pro368= (c.1104G>A) pathogenic?

LFNG p.Pro368= (c.1104G>A) is classified Benign in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Rare (popmax 0.483%, sas); Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Pro368= (c.1104G>A)?

LFNG p.Pro368= (c.1104G>A) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.Pro368= (c.1104G>A) in the general population?

LFNG p.Pro368= (c.1104G>A) is rare (popmax 0.483%, sas) (gnomAD).

LFNG p.Pro368=

c.1104G>A · rs544123371 · VCV715354

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.483%, sas)

Conditions

spondylocostal dysostosis 3, autosomal recessive

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
Pangolin	Δ0.21	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -1.2	GERP -0.77
Overall
CADD	11.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.483% South Asian · 440/91,080 alleles

Filtering AF 0.446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.431%

Overall 0.0329% 530/1,612,920 alleles · rare exomes 505/1,460,738 · genomes 25/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.483%	207
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Middle Eastern	0.0165%	6,058
East Asian	0.00892%	11,216
Admixed American	0.00833%	12,003
European (non-Finnish)	0.00542%	18,437
African / African-American	0.004%	24,994

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.Pro368=
Coding: c.1104G>A
MANE Select: NM_001040167
dbSNP: rs544123371
Type: single nucleotide variant
Location: chr7:2527176 (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-pro368 (accessed [today's date]).

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