Is ETV6 p.Pro204= (c.612C>G) pathogenic?

ETV6 p.Pro204= (c.612C>G) is classified Likely benign in ETV6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-16). Very rare (popmax 0.00934%, afr); Associated with Inborn genetic diseases.

What condition is associated with ETV6 p.Pro204= (c.612C>G)?

ETV6 p.Pro204= (c.612C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ETV6 p.Pro204= (c.612C>G) in the general population?

ETV6 p.Pro204= (c.612C>G) is very rare (popmax 0.00934%, afr) (gnomAD).

ETV6 p.Pro204=

c.612C>G · rs770038030 · VCV3031072

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

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 -0.29	GERP -3.1, phastCons 0.12
Overall
CADD	5.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,920 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00434% 70/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,703
South Asian	0.00878%	11,386
East Asian	0.00668%	14,963
European (non-Finnish)	0.00424%	23,601
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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.Pro204=
Coding: c.612C>G
MANE Select: NM_001987
dbSNP: rs770038030
Type: single nucleotide variant
Location: chr12:11869572 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.61 · 43 PDB
Residue 204: the 'disordered' region

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.Pro204Ala Uncertain significance ★ ⚠ same residue
ETV6 p.Pro204_Leu205insArgSerPro Uncertain significance ★★ same residue
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

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-pro204 (accessed [today's date]).

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