Is LIMA1 p.Ser601Phe (c.1802C>T) pathogenic?

LIMA1 p.Ser601Phe (c.1802C>T) is classified Uncertain significance in LIMA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.1607); Very rare (popmax 0.000679%, nfe).

How common is LIMA1 p.Ser601Phe (c.1802C>T) in the general population?

LIMA1 p.Ser601Phe (c.1802C>T) is very rare (popmax 0.000679%, nfe) (gnomAD).

What do computational predictors say about LIMA1 p.Ser601Phe (c.1802C>T)?

AlphaMissense predicts likely benign (score 0.1607) — an in-silico prediction, not a clinical call.

LIMA1 p.Ser601Phe

c.1802C>T · VCV3867203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000679%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1607	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 72 kb · p 4.7e-05 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000679% European (non-Finnish) · 8/1,179,050 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,611,566 alleles · very rare exomes 8/1,459,214 · genomes 0/152,352 · joint denominator

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: LIMA1
Protein: p.Ser601Phe
Coding: c.1802C>T
MANE Select: NM_016357
Type: single nucleotide variant
Location: chr12:50177542 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.12 · 1 PDB
Residue 601: a modified residue (phosphoserine); the 'disordered' region

Full LIMA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LIMA1 p.Ala113Gly Uncertain significance ★ ⚠ same type
LIMA1 p.Ala136Val Uncertain significance ★ ⚠ same type
LIMA1 p.Ala183Asp Uncertain significance ★ ⚠ same type
LIMA1 p.Ala214Ser Uncertain significance ★ ⚠ same type
LIMA1 p.Ala367Val Uncertain significance ★ ⚠ same type
LIMA1 p.Ala479Val Uncertain significance ★ ⚠ same type
LIMA1 p.Ala531Thr Uncertain significance ★ ⚠ same type
LIMA1 p.Arg141Gln 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/lima1-p-ser601phe (accessed [today's date]).

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