Is LFNG p.Ser274= (c.822C>T) pathogenic?

LFNG p.Ser274= (c.822C>T) is classified Likely benign in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). Ultra-rare (popmax 0.0263%, sas); Associated with Inborn genetic diseases.

What condition is associated with LFNG p.Ser274= (c.822C>T)?

LFNG p.Ser274= (c.822C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LFNG p.Ser274= (c.822C>T) in the general population?

LFNG p.Ser274= (c.822C>T) is ultra-rare (popmax 0.0263%, sas) (gnomAD).

LFNG p.Ser274=

c.822C>T · VCV4046930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, sas)

Conditions

Inborn genetic diseases

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 -11	GERP -3.5
Overall
CADD	0.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0263% South Asian · 24/91,082 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.0036% 58/1,612,872 alleles · ultra-rare exomes 47/1,460,540 · genomes 11/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0263%	3,795
African / African-American	0.0107%	9,381
Admixed American	0.00333%	30,016
European (non-Finnish)	0.00186%	53,635
Remaining individualsnot grpmax-eligible	0.0016%	62,492
Finnishnot grpmax-eligible	0.00159%	62,810

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.Ser274=
Coding: c.822C>T
MANE Select: NM_001040167
Type: single nucleotide variant
Location: chr7:2526244 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LFNG p.Ala99Thr Uncertain significance ★★ ⚠ same condition
LFNG p.Arg187Cys Uncertain significance ★★ ⚠ same condition
LFNG p.Arg341Gln Uncertain significance ★★ ⚠ same condition
LFNG p.Arg4Cys Uncertain significance ★★ ⚠ same condition
LFNG p.Asp231Asn Uncertain significance ★★ ⚠ same condition
LFNG p.Glu190Val Uncertain significance ★★ ⚠ same condition
LFNG p.Pro34Thr Uncertain significance ★★ ⚠ same condition
LFNG p.Pro96Arg 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-ser274 (accessed [today's date]).

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