Is LFNG p.His102= (c.306C>T) pathogenic?

LFNG p.His102= (c.306C>T) is classified Likely benign in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-03). Very rare (popmax 0.00202%, amr); Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.His102= (c.306C>T)?

LFNG p.His102= (c.306C>T) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.His102= (c.306C>T) in the general population?

LFNG p.His102= (c.306C>T) is very rare (popmax 0.00202%, amr) (gnomAD).

LFNG p.His102=

c.306C>T · rs758946205 · VCV2956413

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00202%, amr)

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
Constraint at this position
Conservation	phyloP -0.17	GERP -1.8
Overall
CADD	6.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00202% Admixed American · 1/49,436 alleles

Overall 6.56e-05% 1/1,524,042 alleles · very rare exomes 0/1,372,758 · genomes 1/151,284 · joint denominator

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.His102=
Coding: c.306C>T
MANE Select: NM_001040167
dbSNP: rs758946205
Type: single nucleotide variant
Location: chr7:2520167 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.66
Residue 102: the 'disordered' region

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.His102Gln Uncertain significance ★ ⚠ same residue
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

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-his102 (accessed [today's date]).

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