Is LFNG p.Ala343= (c.1029C>T) pathogenic?

LFNG p.Ala343= (c.1029C>T) is classified Likely benign in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). Very rare (popmax 0.00501%, amr); Associated with spondylocostal dysostosis 3, autosomal recessive.

What condition is associated with LFNG p.Ala343= (c.1029C>T)?

LFNG p.Ala343= (c.1029C>T) is associated with spondylocostal dysostosis 3, autosomal recessive (ClinVar).

How common is LFNG p.Ala343= (c.1029C>T) in the general population?

LFNG p.Ala343= (c.1029C>T) is very rare (popmax 0.00501%, amr) (gnomAD).

LFNG p.Ala343=

c.1029C>T · rs749597262 · VCV2413368

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00501%, 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 -16	GERP -3
Overall
CADD	1.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00501% Admixed American · 3/59,932 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00167% 27/1,612,074 alleles · very rare exomes 25/1,460,478 · genomes 2/151,596 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,977
Remaining individualsnot grpmax-eligible	0.0032%	31,227
European (non-Finnish)	0.00178%	56,185
South Asian	0.0011%	91,050

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.Ala343=
Coding: c.1029C>T
MANE Select: NM_001040167
dbSNP: rs749597262
Type: single nucleotide variant
Location: chr7:2526877 (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-ala343 (accessed [today's date]).

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