Is ENGASE p.Val160Ile (c.478G>A) pathogenic?

ENGASE p.Val160Ile (c.478G>A) is classified Likely benign in ENGASE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely benign (0.0567); Ultra-rare (popmax 0.0165%, mid).

How common is ENGASE p.Val160Ile (c.478G>A) in the general population?

ENGASE p.Val160Ile (c.478G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ENGASE p.Val160Ile (c.478G>A)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

ENGASE p.Val160Ile

c.478G>A · rs538416262 · VCV2253006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.046	GERP -3.8, phastCons 0.006
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	0.398	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00105% 17/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
East Asian	0.00668%	14,959
South Asian	0.0022%	45,537
Finnishnot grpmax-eligible	0.00156%	63,956
African / African-American	0.00133%	75,040
European (non-Finnish)	0.000763%	131,113

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: ENGASE
Protein: p.Val160Ile
Coding: c.478G>A
MANE Select: NM_001042573
dbSNP: rs538416262
Type: single nucleotide variant
Location: chr17:79079550 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41

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

Similar variants

ENGASE p.Val160Leu Uncertain significance ★ ⚠ same residue
ENGASE p.Arg555His Benign ★★ same type
ENGASE c.873-1G>A Uncertain significance ★ same type
ENGASE p.Ala107Val Uncertain significance ★ ⚠ same type
ENGASE p.Ala217Asp Uncertain significance ★ ⚠ same type
ENGASE p.Ala244Val Uncertain significance ★ ⚠ same type
ENGASE p.Ala24Gly Uncertain significance ★ ⚠ same type
ENGASE p.Ala420Val Uncertain significance ★ ⚠ 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/engase-p-val160ile (accessed [today's date]).

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