Is ERGIC2 p.Asn179Ser (c.536A>G) pathogenic?

ERGIC2 p.Asn179Ser (c.536A>G) is classified Uncertain significance in ERGIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). AlphaMissense: likely benign (0.2236); Very rare (popmax 0.00667%, amr).

How common is ERGIC2 p.Asn179Ser (c.536A>G) in the general population?

ERGIC2 p.Asn179Ser (c.536A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ERGIC2 p.Asn179Ser (c.536A>G)?

AlphaMissense predicts likely benign (score 0.2236) — an in-silico prediction, not a clinical call.

ERGIC2 p.Asn179Ser

c.536A>G · VCV3510069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2236 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2236	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 30 kb · p 0.0048 · regional, not allelic
Overall
CADD	28.4	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 0.00667% Admixed American · 4/60,008 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00131% 19/1,449,950 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
South Asian	0.0022%	45,412
Finnishnot grpmax-eligible	0.00156%	64,022
European (non-Finnish)	0.00103%	97,437

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.Asn179Ser
Coding: c.536A>G
MANE Select: NM_016570
Type: single nucleotide variant
Location: chr12:29356418 (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 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.Asn356Ser Uncertain significance ★ ⚠ same type
ERGIC2 p.Asn375Ser 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-asn179ser (accessed [today's date]).

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