Is ENGASE p.Pro116Thr (c.346C>A) pathogenic?

ENGASE p.Pro116Thr (c.346C>A) is classified Uncertain significance in ENGASE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: ambiguous (0.3766); Absent from gnomAD v4.1.

How common is ENGASE p.Pro116Thr (c.346C>A) in the general population?

ENGASE p.Pro116Thr (c.346C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENGASE p.Pro116Thr (c.346C>A)?

AlphaMissense predicts ambiguous (score 0.3766) — an in-silico prediction, not a clinical call.

ENGASE p.Pro116Thr

c.346C>A · rs780658619 · VCV3088875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3766 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3766	ambiguous
REVEL	0.115	moderately benign-leaning
SaProt	LLR -10.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ENGASE
Protein: p.Pro116Thr
Coding: c.346C>A
MANE Select: NM_001042573
dbSNP: rs780658619
Type: single nucleotide variant
Location: chr17:79077794 (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.Pro116Ala 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-pro116thr (accessed [today's date]).

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