Is GTF2E2 p.Ser68= (c.204A>G) pathogenic?

GTF2E2 p.Ser68= (c.204A>G) is classified Likely benign in GTF2E2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). Very rare (popmax 0.0011%, sas).

How common is GTF2E2 p.Ser68= (c.204A>G) in the general population?

GTF2E2 p.Ser68= (c.204A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

GTF2E2 p.Ser68=

c.204A>G · VCV4732397

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.092	GERP -5.5, phastCons 0.71
Overall
CADD	7.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,874 alleles

Overall 0.000249% 4/1,608,612 alleles · very rare exomes 3/1,456,396 · genomes 1/152,216 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00471%	21,251
South Asiangrpmax	0.0011%	90,874

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: GTF2E2
Protein: p.Ser68=
Coding: c.204A>G
MANE Select: NM_002095
Type: single nucleotide variant
Location: chr8:30635086 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 68.97 · 46 PDB
Residue 68: a DNA-binding region; an α-helix

Full GTF2E2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GTF2E2 p.Ser68Pro Uncertain significance ★ ⚠ same residue
GTF2E2 p.Ala138Thr Uncertain significance ★★ ⚠ same type
GTF2E2 p.Ala278Ser Uncertain significance ★★ ⚠ same type
GTF2E2 p.Arg25Cys Uncertain significance ★★ ⚠ same type
GTF2E2 p.Arg269Cys Uncertain significance ★★ ⚠ same type
GTF2E2 p.Gly47Ala Uncertain significance ★★ ⚠ same type
GTF2E2 p.His158Arg Uncertain significance ★★ ⚠ same type
GTF2E2 p.Lys197Arg 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/gtf2e2-p-ser68 (accessed [today's date]).

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