Is LFNG p.Pro247= (c.741T>C) pathogenic?

LFNG p.Pro247= (c.741T>C) is classified Likely benign in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). Rare (popmax 0.125%, eas); Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Pro247= (c.741T>C)?

LFNG p.Pro247= (c.741T>C) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.Pro247= (c.741T>C) in the general population?

LFNG p.Pro247= (c.741T>C) is rare (popmax 0.125%, eas) (gnomAD).

LFNG p.Pro247=

c.741T>C · rs200772027 · VCV2897824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.125%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.3	GERP -3.1
Overall
CADD	1.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.125% East Asian · 56/44,876 alleles

Filtering AF 0.0986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0892%

Overall 0.00353% 57/1,613,242 alleles · rare exomes 51/1,460,868 · genomes 6/152,374 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.125%	801
South Asian	0.0011%	91,078

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.Pro247=
Coding: c.741T>C
MANE Select: NM_001040167
dbSNP: rs200772027
Type: single nucleotide variant
Location: chr7:2525690 (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-pro247 (accessed [today's date]).

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