Is LFNG p.Ser324= (c.972G>A) pathogenic?

LFNG p.Ser324= (c.972G>A) is classified Benign in LFNG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 6.51%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Ser324= (c.972G>A)?

LFNG p.Ser324= (c.972G>A) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

LFNG p.Ser324=

Q: How common is LFNG p.Ser324= (c.972G>A) in the general population?

LFNG p.Ser324= (c.972G>A) is common (popmax 6.51%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.972G>A · rs12700028 · VCV257271

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.51%, nfe) — too common for a highly-penetrant pathogenic allele

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	Δ0.22	gain · loss 0.13 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -15	GERP -3.1
Overall
CADD	0.429	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.51% European (non-Finnish) · 76,758/1,179,836 alleles

Filtering AF 6.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.45%

Overall 5.54% 89,159/1,608,466 alleles · common exomes 82,998/1,456,316 · genomes 6,161/152,150 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	6.51%	15
Finnishnot grpmax-eligible	4.82%	21
Remaining individualsnot grpmax-eligible	4.82%	21
Admixed American	4.46%	22
Ashkenazi Jewishnot grpmax-eligible	3.96%	25
South Asian	2.01%	50
Amishnot grpmax-eligible	1.32%	76
Middle Eastern	1.27%	79
African / African-American	1.02%	98
East Asian	0.0713%	1,402

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.Ser324=
Coding: c.972G>A
MANE Select: NM_001040167
dbSNP: rs12700028
Type: single nucleotide variant
Location: chr7:2526394 (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-ser324 (accessed [today's date]).

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