Is LSM14A p.Pro399Ser (c.1195C>T) pathogenic?

LSM14A p.Pro399Ser (c.1195C>T) is classified Uncertain significance in LSM14A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely pathogenic (0.6924); Absent from gnomAD v4.1.

How common is LSM14A p.Pro399Ser (c.1195C>T) in the general population?

LSM14A p.Pro399Ser (c.1195C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LSM14A p.Pro399Ser (c.1195C>T)?

AlphaMissense predicts likely pathogenic (score 0.6924) — an in-silico prediction, not a clinical call.

LSM14A p.Pro399Ser

c.1195C>T · rs1429810985 · VCV3121310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6924	likely pathogenic
REVEL	0.248	benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 33 kb · p 2.9e-06 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LSM14A
Protein: p.Pro399Ser
Coding: c.1195C>T
MANE Select: NM_015578
dbSNP: rs1429810985
Type: single nucleotide variant
Location: chr19:34221565 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 1 PDB
Residue 399: the 'disordered' region

Full LSM14A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LSM14A c.1369-950C>T Uncertain significance ★ ⚠ same type
LSM14A p.Ala161Gly Uncertain significance ★ ⚠ same type
LSM14A p.Ala161Val Uncertain significance ★ ⚠ same type
LSM14A p.Ala202Thr Uncertain significance ★ ⚠ same type
LSM14A p.Ala264Val Uncertain significance ★ ⚠ same type
LSM14A p.Ala386Thr Uncertain significance ★ ⚠ same type
LSM14A p.Arg181His Uncertain significance ★ ⚠ same type
LSM14A p.Arg276Gln 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/lsm14a-p-pro399ser (accessed [today's date]).

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