Is EEIG2 p.Met2Lys (c.5T>A) pathogenic?

EEIG2 p.Met2Lys (c.5T>A) is classified Uncertain significance in EEIG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.6693); Very rare (popmax 0.0027%, afr).

How common is EEIG2 p.Met2Lys (c.5T>A) in the general population?

EEIG2 p.Met2Lys (c.5T>A) is very rare (popmax 0.0027%, afr) (gnomAD).

What do computational predictors say about EEIG2 p.Met2Lys (c.5T>A)?

AlphaMissense predicts likely pathogenic (score 0.6693) — an in-silico prediction, not a clinical call.

EEIG2 p.Met2Lys

c.5T>A · VCV4246831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6693	likely pathogenic
REVEL	0.229	benign-leaning
SaProt	LLR -9.69	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 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 75 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	24.8	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 0.0027% African / African-American · 2/74,152 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00168% 27/1,607,396 alleles · very rare exomes 27/1,455,710 · genomes 0/151,686 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,076
European (non-Finnish)	0.00212%	47,079

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: EEIG2
Protein: p.Met2Lys
Coding: c.5T>A
MANE Select: NM_001010883
Type: single nucleotide variant
Location: chr1:108560433 (GRCh38)
Structure: AlphaFold pLDDT 70.80
Residue 2: the c2 nt-type domain

Full EEIG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEIG2 p.Ala100Thr Uncertain significance ★ ⚠ same type
EEIG2 p.Arg360His Uncertain significance ★ ⚠ same type
EEIG2 p.Asn25Ser Uncertain significance ★ ⚠ same type
EEIG2 p.Asp123Asn Uncertain significance ★ ⚠ same type
EEIG2 p.Asp12Asn Uncertain significance ★ ⚠ same type
EEIG2 p.Asp255Gly Uncertain significance ★ ⚠ same type
EEIG2 p.Asp287Val Uncertain significance ★ ⚠ same type
EEIG2 p.Asp319His 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/eeig2-p-met2lys (accessed [today's date]).

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