Is EMC8 p.Pro200Thr (c.598C>A) pathogenic?

EMC8 p.Pro200Thr (c.598C>A) is classified Uncertain significance in EMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-12). AlphaMissense: likely pathogenic (0.5835); Absent from gnomAD v4.1.

How common is EMC8 p.Pro200Thr (c.598C>A) in the general population?

EMC8 p.Pro200Thr (c.598C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC8 p.Pro200Thr (c.598C>A)?

AlphaMissense predicts likely pathogenic (score 0.5835) — an in-silico prediction, not a clinical call.

EMC8 p.Pro200Thr

c.598C>A · VCV3275275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5835	likely pathogenic
REVEL	0.26	benign-leaning
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.73 · regional, not allelic
Overall
CADD	28.3	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: EMC8
Protein: p.Pro200Thr
Coding: c.598C>A
MANE Select: NM_006067
Type: single nucleotide variant
Location: chr16:85779743 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 91.60 · 9 PDB
Residue 200: an α-helix

Full EMC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC8 p.Ala25Val Uncertain significance ★ ⚠ same type
EMC8 p.Ala32Val Uncertain significance ★ ⚠ same type
EMC8 p.Asp84Val Uncertain significance ★ ⚠ same type
EMC8 p.Glu181Lys Uncertain significance ★ ⚠ same type
EMC8 p.Gly3Trp Uncertain significance ★ ⚠ same type
EMC8 p.His85Arg Uncertain significance ★ ⚠ same type
EMC8 p.Ile125Val Uncertain significance ★ ⚠ same type
EMC8 p.Leu29Pro 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/emc8-p-pro200thr (accessed [today's date]).

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