Is ENG p.Gln176Ter (c.526C>T) pathogenic?

ENG p.Gln176Ter (c.526C>T) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-17). Absent from gnomAD v4.1.

How common is ENG p.Gln176Ter (c.526C>T) in the general population?

ENG p.Gln176Ter (c.526C>T) is absent from gnomAD v4.1 (gnomAD).

ENG p.Gln176Ter

c.526C>T · rs1131691674 · VCV429922

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,198)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 15
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.39	GERP -1.7, phastCons 0.011
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,198). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENG
Protein: p.Gln176Ter
Coding: c.526C>T
MANE Select: NM_001114753
dbSNP: rs1131691674
Type: single nucleotide variant
Location: chr9:127825858 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 176: a disulfide bond; the 'required for interaction with gdf2' region; the 'or2' region

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

Similar variants

ENG p.Gln176fs Pathogenic ★ same residue
ENG p.Arg529His Pathogenic ★★★ same type
ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same type
ENG p.Cys382Tyr Pathogenic ★★★ same type
ENG p.Cys549Gly Likely pathogenic ★★★ same type
ENG p.Gly331Ser Pathogenic ★★★ ⚠ same type
ENG p.Gly603Arg Likely pathogenic ★★★ same type
ENG p.Leu221Pro Likely pathogenic ★★★ 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/eng-p-gln176ter (accessed [today's date]).

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