Is ETV6 p.Ser365= (c.1095C>T) pathogenic?

ETV6 p.Ser365= (c.1095C>T) is classified Conflicting classifications of pathogenicity in ETV6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-05). Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with ETV6 p.Ser365= (c.1095C>T)?

ETV6 p.Ser365= (c.1095C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ETV6 p.Ser365= (c.1095C>T) in the general population?

ETV6 p.Ser365= (c.1095C>T) is very rare (popmax 0.005%, amr) (gnomAD).

ETV6 p.Ser365=

c.1095C>T · rs369012954 · VCV2893100

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.78, phastCons 1
Overall
CADD	12.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000929% 15/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
African / African-American	0.00133%	74,912
European (non-Finnish)	0.000932%	107,275

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: ETV6
Protein: p.Ser365=
Coding: c.1095C>T
MANE Select: NM_001987
dbSNP: rs369012954
Type: single nucleotide variant
Location: chr12:11884530 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.61 · 43 PDB
Residue 365: a DNA-binding region; an α-helix

Full ETV6 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

ETV6 p.Arg359Ter Pathogenic ★★ same condition
ETV6 p.Arg369Gln Pathogenic/Likely pathogenic ★★ same condition
ETV6 c.1010-3T>C Uncertain significance ★★ same condition
ETV6 p.Ala247Gly Uncertain significance ★★ ⚠ same condition
ETV6 p.Ala67Asp Uncertain significance ★★ ⚠ same condition
ETV6 p.Ala73Ser Uncertain significance ★★ ⚠ same condition
ETV6 p.Arg127Trp Uncertain significance ★★ ⚠ same condition
ETV6 p.Arg14Gln 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/etv6-p-ser365 (accessed [today's date]).

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