Is EIF5 p.Asn77Ser (c.230A>G) pathogenic?

EIF5 p.Asn77Ser (c.230A>G) is classified Uncertain significance in EIF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely pathogenic (0.9922); Very rare (popmax 0.000169%, nfe).

How common is EIF5 p.Asn77Ser (c.230A>G) in the general population?

EIF5 p.Asn77Ser (c.230A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about EIF5 p.Asn77Ser (c.230A>G)?

AlphaMissense predicts likely pathogenic (score 0.9922) — an in-silico prediction, not a clinical call.

EIF5 p.Asn77Ser

c.230A>G · VCV4017315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9922	likely pathogenic
REVEL	0.541	indeterminate
SaProt	LLR -14.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 2,468 bp · p 4.9e-09 · regional, not allelic
Overall
CADD	25.7	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 0.000169% European (non-Finnish) · 2/1,180,026 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,880 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: EIF5
Protein: p.Asn77Ser
Coding: c.230A>G
MANE Select: NM_001969
Type: single nucleotide variant
Location: chr14:103336752 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 6 PDB
Residue 77: a β-strand

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-asn77ser (accessed [today's date]).

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