Is EIF5A p.Pro115Ser (c.343C>T) pathogenic?

EIF5A p.Pro115Ser (c.343C>T) is classified Likely pathogenic in EIF5A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-03). AlphaMissense: likely pathogenic (0.9454); Absent from gnomAD v4.1.

How common is EIF5A p.Pro115Ser (c.343C>T) in the general population?

EIF5A p.Pro115Ser (c.343C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF5A p.Pro115Ser (c.343C>T)?

AlphaMissense predicts likely pathogenic (score 0.9454) — an in-silico prediction, not a clinical call.

EIF5A p.Pro115Ser

c.343C>T · rs2143009616 · VCV1327680

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9454 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9454	likely pathogenic ✓ concordant with ClinVar
REVEL	0.341	indeterminate
SaProt	LLR -13.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.15	constrained · MANE · 2,001 bp · p 8e-33 · regional, not allelic
Overall
CADD	28.9	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: EIF5A
Protein: p.Pro115Ser
Coding: c.343C>T
MANE Select: NM_001970
dbSNP: rs2143009616
Type: single nucleotide variant
Location: chr17:7311422 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.07 · 4 PDB
Residue 115: a UniProt-annotated variant site (in fabas); an α-helix

Full EIF5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF5A p.Pro115fs Likely pathogenic ★ same residue
EIF5A p.Arg109Ter Pathogenic/Likely pathogenic ★★ same type
EIF5A p.Arg26Pro Likely pathogenic ★★ same type
EIF5A c.69+1G>A Uncertain significance ★★ same type
EIF5A c.165+1G>A Likely pathogenic ★ same type
EIF5A c.270+1G>A Likely pathogenic ★ same type
EIF5A p.Glu42Lys Likely pathogenic ★ same type
EIF5A p.Gly106Arg Pathogenic ★ 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/eif5a-p-pro115ser (accessed [today's date]).

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