Is ENG p.Gln297= (c.891A>G) pathogenic?

ENG p.Gln297= (c.891A>G) is classified Likely benign in ENG (ClinVar, Single submitter, 2 submitters; last evaluated 2023-02-16). Very rare (popmax 0.00534%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Gln297= (c.891A>G)?

ENG p.Gln297= (c.891A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Gln297= (c.891A>G) in the general population?

ENG p.Gln297= (c.891A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

ENG p.Gln297=

c.891A>G · rs770899669 · VCV3035938

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Cardiovascular phenotype

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 -0.81	GERP -2.8, phastCons 0.02
Overall
CADD	6.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,866 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,613,812 alleles · very rare exomes 4/1,461,758 · genomes 2/152,054 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,716
Admixed American	0.00333%	29,985

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: ENG
Protein: p.Gln297=
Coding: c.891A>G
MANE Select: NM_001114753
dbSNP: rs770899669
Type: single nucleotide variant
Location: chr9:127824900 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 297: an α-helix; the 'required for interaction with gdf2' region; the 'or1, c-terminal part' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ENG p.Gln297Glu Uncertain significance ★★ ⚠ same residue
ENG p.Gln297Ter Likely pathogenic ★ same residue
ENG c.1134+1G>T Pathogenic/Likely pathogenic ★★ same condition
ENG c.1311+2T>A Pathogenic ★★ same condition
ENG c.1428+1G>A Pathogenic/Likely pathogenic ★★ same condition
ENG c.1687-1G>A Pathogenic/Likely pathogenic ★★ same condition
ENG c.219+1G>A Pathogenic ★★ same condition
ENG c.219+2T>C Pathogenic/Likely pathogenic ★★ 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/eng-p-gln297 (accessed [today's date]).

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