Is LONP1 p.Pro613Ser (c.1837C>T) pathogenic?

LONP1 p.Pro613Ser (c.1837C>T) is classified Conflicting classifications of pathogenicity in LONP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-17). AlphaMissense: likely pathogenic (0.8677); Ultra-rare (popmax 0.0916%, amr); Associated with Inborn genetic diseases.

What condition is associated with LONP1 p.Pro613Ser (c.1837C>T)?

LONP1 p.Pro613Ser (c.1837C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LONP1 p.Pro613Ser (c.1837C>T) in the general population?

LONP1 p.Pro613Ser (c.1837C>T) is ultra-rare (popmax 0.0916%, amr) (gnomAD).

What do computational predictors say about LONP1 p.Pro613Ser (c.1837C>T)?

AlphaMissense predicts likely pathogenic (score 0.8677) — an in-silico prediction, not a clinical call.

LONP1 p.Pro613Ser

c.1837C>T · rs535918140 · VCV1372235

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8677 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0916%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8677	likely pathogenic
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 4,687 bp · p 0.6 · regional, not allelic
Overall
CADD	31.0	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 0.0916% Admixed American · 55/60,018 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0653%

Overall 0.00378% 61/1,613,414 alleles · ultra-rare exomes 29/1,461,114 · genomes 32/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0916%	1,091
Remaining individualsnot grpmax-eligible	0.0048%	20,830
European (non-Finnish)	0.000254%	393,301

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: LONP1
Protein: p.Pro613Ser
Coding: c.1837C>T
MANE Select: NM_004793
dbSNP: rs535918140
Type: single nucleotide variant
Location: chr19:5696308 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.35 · 36 PDB
Residue 613: an α-helix

Full LONP1 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

LONP1 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
LONP1 p.Ala337Thr Uncertain significance ★★ ⚠ same condition
LONP1 p.Ala901Val Uncertain significance ★★ ⚠ same condition
LONP1 p.Arg422Trp Uncertain significance ★★ ⚠ same condition
LONP1 p.Arg424Cys Uncertain significance ★★ ⚠ same condition
LONP1 p.Arg546His Uncertain significance ★★ ⚠ same condition
LONP1 p.Arg679Cys Uncertain significance ★★ ⚠ same condition
LONP1 p.Asn354Ser 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/lonp1-p-pro613ser (accessed [today's date]).

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