Is EFTUD2 p.Thr526= (c.1578C>T) pathogenic?

EFTUD2 p.Thr526= (c.1578C>T) is classified Benign/Likely benign in EFTUD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-27). Ultra-rare (popmax 0.033%, mid).

How common is EFTUD2 p.Thr526= (c.1578C>T) in the general population?

EFTUD2 p.Thr526= (c.1578C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

EFTUD2 p.Thr526=

c.1578C>T · rs150104145 · VCV1234486

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 · G>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.4	GERP -5.5
Overall
CADD	1.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00874% 141/1,613,868 alleles · ultra-rare exomes 123/1,461,680 · genomes 18/152,188 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.196%	510
Middle Easterngrpmax	0.033%	3,031
Admixed American	0.0233%	4,285
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.00659%	15,177
European (non-Finnish)	0.00432%	23,135
African / African-American	0.004%	24,997

Ashkenazi Jewish 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: EFTUD2
Protein: p.Thr526=
Coding: c.1578C>T
MANE Select: NM_004247
dbSNP: rs150104145
Type: single nucleotide variant
Location: chr17:44862742 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 526: a β-strand

Full EFTUD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFTUD2 c.1058+1G>A Pathogenic ★★ same type
EFTUD2 c.1414-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.1607+1G>T Likely pathogenic ★★ same type
EFTUD2 c.1962+1G>A Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.2133-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.2562-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.703-2A>G 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/eftud2-p-thr526 (accessed [today's date]).

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