Is ELOC p.Met75Val (c.223A>G) pathogenic?

ELOC p.Met75Val (c.223A>G) is classified Uncertain significance in ELOC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.4019); Absent from gnomAD v4.1.

How common is ELOC p.Met75Val (c.223A>G) in the general population?

ELOC p.Met75Val (c.223A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELOC p.Met75Val (c.223A>G)?

AlphaMissense predicts ambiguous (score 0.4019) — an in-silico prediction, not a clinical call.

ELOC p.Met75Val

c.223A>G · VCV4663965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4019 · 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	0.4019	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -12.35	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 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 13 kb · p 1e-17 · regional, not allelic
Overall
CADD	21.1	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: ELOC
Protein: p.Met75Val
Coding: c.223A>G
MANE Select: NM_005648
Type: single nucleotide variant
Location: chr8:73946746 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 90.10 · 192 PDB
Residue 75: an α-helix

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

Similar variants

ELOC p.Ala96Gly Uncertain significance ★ ⚠ same type
ELOC p.Glu4Lys Uncertain significance ★ ⚠ same type
ELOC p.Ile22Leu Uncertain significance ★ ⚠ same type
ELOC p.Leu21Val 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/eloc-p-met75val (accessed [today's date]).

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