Is EEF1B2 p.Ser43Arg (c.129C>G) pathogenic?

EEF1B2 p.Ser43Arg (c.129C>G) is classified Uncertain significance in EEF1B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.2064); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with EEF1B2 p.Ser43Arg (c.129C>G)?

EEF1B2 p.Ser43Arg (c.129C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EEF1B2 p.Ser43Arg (c.129C>G) in the general population?

EEF1B2 p.Ser43Arg (c.129C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EEF1B2 p.Ser43Arg (c.129C>G)?

AlphaMissense predicts likely benign (score 0.2064) — an in-silico prediction, not a clinical call.

EEF1B2 p.Ser43Arg

c.129C>G · VCV4016300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2064	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -4.2, phastCons 0.036
Regional constraint	o/e 1.03	unconstrained · MANE · 2,538 bp · p 0.72 · regional, not allelic
Overall
CADD	14.4	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 0.00223% East Asian · 1/44,844 alleles

Overall 6.84e-05% 1/1,461,882 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: EEF1B2
Protein: p.Ser43Arg
Coding: c.129C>G
MANE Select: NM_001959
Type: single nucleotide variant
Location: chr2:206160636 (GRCh38)
Gene constraint: LOEUF 0.688 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 77.83 · 2 PDB
Residue 43: the gst c-terminal domain

Full EEF1B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EEF1B2 p.Ala115Thr Uncertain significance ★ ⚠ same condition
EEF1B2 p.Ala167Thr Uncertain significance ★ ⚠ same condition
EEF1B2 p.Asp108Glu Uncertain significance ★ ⚠ same condition
EEF1B2 p.Asp201Glu Uncertain significance ★ ⚠ same condition
EEF1B2 p.Asp21Asn Uncertain significance ★ ⚠ same condition
EEF1B2 p.Asp99Gly Uncertain significance ★ ⚠ same condition
EEF1B2 p.Gln125Leu Uncertain significance ★ ⚠ same condition
EEF1B2 p.Gln190Arg Uncertain significance ★ ⚠ same condition

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/eef1b2-p-ser43arg (accessed [today's date]).

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