Is EEIG2 p.Phe107Leu (c.321T>G) pathogenic?

EEIG2 p.Phe107Leu (c.321T>G) is classified Uncertain significance in EEIG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely pathogenic (0.987); Absent from gnomAD v4.1.

How common is EEIG2 p.Phe107Leu (c.321T>G) in the general population?

EEIG2 p.Phe107Leu (c.321T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEIG2 p.Phe107Leu (c.321T>G)?

AlphaMissense predicts likely pathogenic (score 0.987) — an in-silico prediction, not a clinical call.

EEIG2 p.Phe107Leu

c.321T>G · VCV3506814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.987	likely pathogenic · top 9% in EEIG2
REVEL	0.433	indeterminate
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.14, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 75 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	24.3	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: EEIG2
Protein: p.Phe107Leu
Coding: c.321T>G
MANE Select: NM_001010883
Type: single nucleotide variant
Location: chr1:108612210 (GRCh38)
Structure: AlphaFold pLDDT 70.80
Residue 107: 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-phe107leu (accessed [today's date]).

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