Is EIF5 p.Pro191Ser (c.571C>T) pathogenic?

EIF5 p.Pro191Ser (c.571C>T) is classified Uncertain significance in EIF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0868); Ultra-rare (popmax 0.012%, eas).

How common is EIF5 p.Pro191Ser (c.571C>T) in the general population?

EIF5 p.Pro191Ser (c.571C>T) is ultra-rare (popmax 0.012%, eas) (gnomAD).

What do computational predictors say about EIF5 p.Pro191Ser (c.571C>T)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

EIF5 p.Pro191Ser

c.571C>T · rs779951363 · VCV3088076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP -0.48, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 892 bp · p 0.18 · regional, not allelic
Overall
CADD	21.9	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 0.012% East Asian · 5/41,794 alleles

Filtering AF 0.00471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00303%

Overall 0.00134% 21/1,571,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.012%	8,359
Admixed American	0.00189%	52,892
Finnishnot grpmax-eligible	0.00162%	61,790
European (non-Finnish)	0.00121%	82,707

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: EIF5
Protein: p.Pro191Ser
Coding: c.571C>T
MANE Select: NM_001969
dbSNP: rs779951363
Type: single nucleotide variant
Location: chr14:103338458 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 6 PDB
Residue 191: the 'disordered' region

Full EIF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF5 c.745-8C>T Benign/Likely benign ★★ same type
EIF5 p.Ala124Thr Uncertain significance ★ ⚠ same type
EIF5 p.Ala368Gly Uncertain significance ★ ⚠ same type
EIF5 p.Arg128Gln Uncertain significance ★ ⚠ same type
EIF5 p.Arg214Cys Uncertain significance ★ ⚠ same type
EIF5 p.Arg215Gln Uncertain significance ★ ⚠ same type
EIF5 p.Arg312Trp Uncertain significance ★ ⚠ same type
EIF5 p.Arg372Ser 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/eif5-p-pro191ser (accessed [today's date]).

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