Is ERGIC2 p.Thr152Ala (c.454A>G) pathogenic?

ERGIC2 p.Thr152Ala (c.454A>G) is classified Likely benign in ERGIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.0543); Ultra-rare (popmax 0.0419%, amr).

How common is ERGIC2 p.Thr152Ala (c.454A>G) in the general population?

ERGIC2 p.Thr152Ala (c.454A>G) is ultra-rare (popmax 0.0419%, amr) (gnomAD).

What do computational predictors say about ERGIC2 p.Thr152Ala (c.454A>G)?

AlphaMissense predicts likely benign (score 0.0543) — an in-silico prediction, not a clinical call.

ERGIC2 p.Thr152Ala

c.454A>G · rs200037116 · VCV3090158

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0543 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0419%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0543	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.12	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 -3	GERP -3.7
Regional constraint	o/e 0.87	unconstrained · MANE · 30 kb · p 0.0048 · regional, not allelic
Overall
CADD	7.083	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 0.0419% Admixed American · 25/59,676 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00208% 33/1,588,342 alleles · ultra-rare exomes 31/1,435,990 · genomes 2/152,352 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0419%	2,387
South Asian	0.00554%	18,060
Remaining individualsnot grpmax-eligible	0.00324%	30,826
East Asian	0.00224%	44,648

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: ERGIC2
Protein: p.Thr152Ala
Coding: c.454A>G
MANE Select: NM_016570
dbSNP: rs200037116
Type: single nucleotide variant
Location: chr12:29357645 (GRCh38)
Gene constraint: LOEUF 1.266 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21

Full ERGIC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERGIC2 p.Thr152Ile Uncertain significance ★ ⚠ same residue
ERGIC2 c.572+5G>A Pathogenic ★ same type
ERGIC2 p.Ala240Ser Uncertain significance ★ ⚠ same type
ERGIC2 p.Ala283Glu Uncertain significance ★ ⚠ same type
ERGIC2 p.Arg197Cys Uncertain significance ★ ⚠ same type
ERGIC2 p.Arg277Pro Uncertain significance ★ ⚠ same type
ERGIC2 p.Arg346His Uncertain significance ★ ⚠ same type
ERGIC2 p.Asn179Ser 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/ergic2-p-thr152ala (accessed [today's date]).

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