Is ENG p.Ile429= (c.1287C>A) pathogenic?

ENG p.Ile429= (c.1287C>A) is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Very rare (popmax 0.00134%, afr).

How common is ENG p.Ile429= (c.1287C>A) in the general population?

ENG p.Ile429= (c.1287C>A) is very rare (popmax 0.00134%, afr) (gnomAD).

ENG p.Ile429=

c.1287C>A · VCV3257462

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 1.3	GERP -1.7, phastCons 1
Overall
CADD	6.819	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,898 alleles

Overall 0.000372% 6/1,611,886 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,213
Finnishnot grpmax-eligible	0.00157%	63,858
African / African-Americangrpmax	0.00134%	74,898
South Asian	0.0011%	90,548
European (non-Finnish)	8.48e-05%	1,179,199

Remaining individuals 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: ENG
Protein: p.Ile429=
Coding: c.1287C>A
MANE Select: NM_001114753
Type: single nucleotide variant
Location: chr9:127819646 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 429: a β-strand; a disulfide bond; the zp domain

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

Similar variants

ENG p.Ile429Asn Uncertain significance ★ ⚠ same residue
ENG p.Ile429Thr Uncertain significance ★ ⚠ same residue
ENG p.Ile429Val Uncertain significance ★ ⚠ 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

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-ile429 (accessed [today's date]).

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