Is LCP1 p.Pro601Ser (c.1801C>T) pathogenic?

LCP1 p.Pro601Ser (c.1801C>T) is classified Uncertain significance in LCP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely pathogenic (0.9114); Very rare (popmax 0.000339%, nfe).

How common is LCP1 p.Pro601Ser (c.1801C>T) in the general population?

LCP1 p.Pro601Ser (c.1801C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about LCP1 p.Pro601Ser (c.1801C>T)?

AlphaMissense predicts likely pathogenic (score 0.9114) — an in-silico prediction, not a clinical call.

LCP1 p.Pro601Ser

c.1801C>T · rs2500584015 · VCV2340809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9114	likely pathogenic
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -13.33	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 2.1, phastCons 1
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,020 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,878 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: LCP1
Protein: p.Pro601Ser
Coding: c.1801C>T
MANE Select: NM_014828 · reported on NM_002298
dbSNP: rs2500584015
Type: single nucleotide variant
Location: chr13:46127674 (GRCh38)
Structure: AlphaFold pLDDT 55.51 · 1 PDB
Residue 601: an α-helix

Full LCP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LCP1 p.Ala40Val Benign ★★ same type
LCP1 p.Tyr374Ter Pathogenic ★ same type
LCP1 p.Ala247Val Uncertain significance ★ ⚠ same type
LCP1 p.Ala341Val Uncertain significance ★ ⚠ same type
LCP1 p.Ala389Thr Uncertain significance ★ ⚠ same type
LCP1 p.Ala59Val Uncertain significance ★ ⚠ same type
LCP1 p.Arg141Gln Uncertain significance ★ ⚠ same type
LCP1 p.Arg326Trp 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/lcp1-p-pro601ser (accessed [today's date]).

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