Is EEIG2 p.Ser321Ile (c.962G>T) pathogenic?

EEIG2 p.Ser321Ile (c.962G>T) is classified Uncertain significance in EEIG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.5319); Very rare (popmax 0.00111%, sas).

How common is EEIG2 p.Ser321Ile (c.962G>T) in the general population?

EEIG2 p.Ser321Ile (c.962G>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about EEIG2 p.Ser321Ile (c.962G>T)?

AlphaMissense predicts ambiguous (score 0.5319) — an in-silico prediction, not a clinical call.

EEIG2 p.Ser321Ile

c.962G>T · VCV4246830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5319 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Computational evidence

Protein change
AlphaMissense	0.5319	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -8.57	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 75 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	27.0	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 0.00111% South Asian · 1/90,202 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000959% 14/1,459,232 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,202
European (non-Finnish)	0.0011%	90,687

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.Ser321Ile
Coding: c.962G>T
MANE Select: NM_001010883
Type: single nucleotide variant
Location: chr1:108628796 (GRCh38)
Structure: AlphaFold pLDDT 70.80
Residue 321: a modified residue (phosphoserine)

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

Similar variants

EEIG2 p.Ser321Asn Uncertain significance ★ ⚠ same residue
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

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-ser321ile (accessed [today's date]).

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