Is ETS1 p.Pro12= (c.36C>T) pathogenic?

ETS1 p.Pro12= (c.36C>T) is classified Benign in ETS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 3.82%, afr).

How common is ETS1 p.Pro12= (c.36C>T) in the general population?

ETS1 p.Pro12= (c.36C>T) is low-frequency (popmax 3.82%, afr) (gnomAD).

ETS1 p.Pro12=

c.36C>T · rs145793592 · VCV779381

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.82%, afr)

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 -1.3	GERP -3.7
Overall
CADD	1.878	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.82% African / African-American · 2,855/74,836 alleles

Filtering AF 3.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.65%

Overall 0.384% 6,150/1,602,914 alleles · low-frequency exomes 4,251/1,450,654 · genomes 1,899/152,260 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	5.96%	17
African / African-Americangrpmax	3.82%	26
Remaining individualsnot grpmax-eligible	0.821%	122
Middle Eastern	0.53%	189
Admixed American	0.338%	296
European (non-Finnish)	0.0661%	1,512
South Asian	0.0283%	3,537
East Asian	0.00674%	14,832

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: ETS1
Protein: p.Pro12=
Coding: c.36C>T
MANE Select: NM_001143820
dbSNP: rs145793592
Type: single nucleotide variant
Location: chr11:128573095 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.95 · 21 PDB

Full ETS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ETS1 c.*1736A>G Benign ★★ same type
ETS1 p.Ala151Thr Likely benign ★★ same type
ETS1 p.Arg307= Benign ★★ same type
ETS1 p.Ser200= Benign ★★ same type
ETS1 p.Arg35Ter Likely pathogenic ★ same type
ETS1 p.Ala337Ser Uncertain significance ★ ⚠ same type
ETS1 p.Ala338Val Uncertain significance ★ ⚠ same type
ETS1 p.Ala475Thr 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/ets1-p-pro12 (accessed [today's date]).

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