Is EEF1B2 p.Asp99Gly (c.296A>G) pathogenic?

EEF1B2 p.Asp99Gly (c.296A>G) is classified Uncertain significance in EEF1B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely benign (0.28); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with EEF1B2 p.Asp99Gly (c.296A>G)?

EEF1B2 p.Asp99Gly (c.296A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EEF1B2 p.Asp99Gly (c.296A>G) in the general population?

EEF1B2 p.Asp99Gly (c.296A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about EEF1B2 p.Asp99Gly (c.296A>G)?

AlphaMissense predicts likely benign (score 0.28) — an in-silico prediction, not a clinical call.

EEF1B2 p.Asp99Gly

c.296A>G · rs762476407 · VCV2495425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.28 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.28	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -10.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,538 bp · p 0.72 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000274% 4/1,461,666 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
European (non-Finnish)	8.48e-05%	1,179,888

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.Asp99Gly
Coding: c.296A>G
MANE Select: NM_001959
dbSNP: rs762476407
Type: single nucleotide variant
Location: chr2:206161438 (GRCh38)
Gene constraint: LOEUF 0.688 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 77.83 · 2 PDB
Residue 99: the 'disordered' region

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.Gln125Leu Uncertain significance ★ ⚠ same condition
EEF1B2 p.Gln190Arg Uncertain significance ★ ⚠ same condition
EEF1B2 p.Gln190Glu 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-asp99gly (accessed [today's date]).

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