Is LFNG p.Glu76= (c.228G>A) pathogenic?

LFNG p.Glu76= (c.228G>A) is classified Likely benign in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). No allele count reported in gnomAD v4.1 (AN 1,323,892); Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Glu76= (c.228G>A)?

LFNG p.Glu76= (c.228G>A) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.Glu76= (c.228G>A) in the general population?

LFNG p.Glu76= (c.228G>A) is no allele count reported in gnomAD v4.1 (AN 1,323,892) (gnomAD).

LFNG p.Glu76=

c.228G>A · VCV4809612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,323,892)

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 1.4	GERP -2.1, phastCons 1
Overall
CADD	12.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,323,892). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LFNG
Protein: p.Glu76=
Coding: c.228G>A
MANE Select: NM_001040167
Type: single nucleotide variant
Location: chr7:2520089 (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.Glu76Lys 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-glu76 (accessed [today's date]).

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