Is EIF2B2 p.Ser17= (c.51C>T) pathogenic?

EIF2B2 p.Ser17= (c.51C>T) is classified Likely benign in EIF2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). Very rare (popmax 0.00167%, amr).

How common is EIF2B2 p.Ser17= (c.51C>T) in the general population?

EIF2B2 p.Ser17= (c.51C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

EIF2B2 p.Ser17=

c.51C>T · rs749552337 · VCV2988225

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.65 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.22	GERP -3.8, phastCons 0.99
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00136% 22/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0188%	5,331
Admixed Americangrpmax	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000678%	147,504

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EIF2B2
Protein: p.Ser17=
Coding: c.51C>T
MANE Select: NM_014239
dbSNP: rs749552337
Type: single nucleotide variant
Location: chr14:75003041 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.82 · 38 PDB
Residue 17: an α-helix

Full EIF2B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF2B2 c.285-1G>A Likely pathogenic ★★ same type
EIF2B2 c.832-2A>G Likely pathogenic ★★ same type
EIF2B2 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Glu213Gly Pathogenic ★★ ⚠ same type
EIF2B2 p.Glu304Ter Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Gly200Val Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Lys273Arg Pathogenic/Likely 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/eif2b2-p-ser17 (accessed [today's date]).

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