Is LRFN5 p.Ser192Phe (c.575C>T) pathogenic?

LRFN5 p.Ser192Phe (c.575C>T) is classified Uncertain significance in LRFN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-01-13). AlphaMissense: ambiguous (0.3865); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LRFN5 p.Ser192Phe (c.575C>T)?

LRFN5 p.Ser192Phe (c.575C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRFN5 p.Ser192Phe (c.575C>T) in the general population?

LRFN5 p.Ser192Phe (c.575C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about LRFN5 p.Ser192Phe (c.575C>T)?

AlphaMissense predicts ambiguous (score 0.3865) — an in-silico prediction, not a clinical call.

LRFN5 p.Ser192Phe

c.575C>T · rs869312921 · VCV224999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3865	ambiguous
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -4.57	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 1,018 bp · p 3e-06 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,014 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00116% 17/1,461,806 alleles · very rare

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: LRFN5
Protein: p.Ser192Phe
Coding: c.575C>T
MANE Select: NM_152447
dbSNP: rs869312921
Type: single nucleotide variant
Location: chr14:41887200 (GRCh38)
Gene constraint: LOEUF 0.629 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 74.66 · 4 PDB
Residue 192: a turn

Full LRFN5 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

LRFN5 p.Thr290Ile Uncertain significance ★ ⚠ same condition
LRFN5 p.Ala148Thr Uncertain significance ★ ⚠ same type
LRFN5 p.Ala17Ser Uncertain significance ★ ⚠ same type
LRFN5 p.Ala424Thr Uncertain significance ★ ⚠ same type
LRFN5 p.Ala701Ser Uncertain significance ★ ⚠ same type
LRFN5 p.Arg252Gly Uncertain significance ★ ⚠ same type
LRFN5 p.Arg272His Uncertain significance ★ ⚠ same type
LRFN5 p.Arg462Gly Uncertain significance ★ ⚠ same type

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/lrfn5-p-ser192phe (accessed [today's date]).

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