Is EEIG1 p.Pro73Leu (c.218C>T) pathogenic?

EEIG1 p.Pro73Leu (c.218C>T) is classified Uncertain significance in EEIG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1965); Very rare (popmax 0.0022%, sas).

How common is EEIG1 p.Pro73Leu (c.218C>T) in the general population?

EEIG1 p.Pro73Leu (c.218C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about EEIG1 p.Pro73Leu (c.218C>T)?

AlphaMissense predicts likely benign (score 0.1965) — an in-silico prediction, not a clinical call.

EEIG1 p.Pro73Leu

c.218C>T · VCV4663164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1965	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 32 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000744% 12/1,613,976 alleles · very rare exomes 12/1,461,680 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
African / African-American	0.00133%	75,042
European (non-Finnish)	0.000763%	131,113

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: EEIG1
Protein: p.Pro73Leu
Coding: c.218C>T
MANE Select: NM_001035254
Type: single nucleotide variant
Location: chr9:127953854 (GRCh38)
Structure: AlphaFold pLDDT 69.30
Residue 73: the c2 nt-type domain

Full EEIG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEIG1 p.Ala326Val Uncertain significance ★ ⚠ same type
EEIG1 p.Arg118His Uncertain significance ★ ⚠ same type
EEIG1 p.Arg194Gln Uncertain significance ★ ⚠ same type
EEIG1 p.Arg228Gly Uncertain significance ★ ⚠ same type
EEIG1 p.Arg248Cys Uncertain significance ★ ⚠ same type
EEIG1 p.Arg258His Uncertain significance ★ ⚠ same type
EEIG1 p.Arg259Gly Uncertain significance ★ ⚠ same type
EEIG1 p.Arg283Gln 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/eeig1-p-pro73leu (accessed [today's date]).

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