Is ERI2 p.Arg572His (c.1715G>A) pathogenic?

ERI2 p.Arg572His (c.1715G>A) is classified Likely benign in ERI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.076); Ultra-rare (popmax 0.063%, afr).

How common is ERI2 p.Arg572His (c.1715G>A) in the general population?

ERI2 p.Arg572His (c.1715G>A) is ultra-rare (popmax 0.063%, afr) (gnomAD).

What do computational predictors say about ERI2 p.Arg572His (c.1715G>A)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

ERI2 p.Arg572His

c.1715G>A · rs370390087 · VCV3090184

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.063%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.001	strongly benign-leaning
SaProt	LLR -6.36	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 -0.23	GERP -3.4
Regional constraint	o/e 0.87	unconstrained · MANE · 8,703 bp · p 0.00034 · regional, not allelic
Overall
CADD	0.096	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 0.063% African / African-American · 46/73,004 alleles

Filtering AF 0.0485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0434%

Overall 0.0102% 159/1,551,348 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.063%	1,587
Ashkenazi Jewishnot grpmax-eligible	0.0593%	1,685
Middle Eastern	0.0166%	6,014
Remaining individualsnot grpmax-eligible	0.015%	6,677
European (non-Finnish)	0.00706%	14,159
Admixed American	0.00393%	25,474
South Asian	0.00357%	28,015

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: ERI2
Protein: p.Arg572His
Coding: c.1715G>A
MANE Select: NM_001142725
dbSNP: rs370390087
Type: single nucleotide variant
Location: chr16:20798085 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.66 · 2 PDB

Full ERI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERI2 p.Arg572Cys Uncertain significance ★ ⚠ same residue
ACSM3 p.Asn444His Uncertain significance ★ ⚠ same type
ACSM3 p.Gly260Ala Uncertain significance ★ ⚠ same type
ACSM3 p.Pro268Arg Uncertain significance ★ ⚠ same type
ACSM3 p.Trp273Arg Uncertain significance ★ ⚠ same type
ACSM3 p.Tyr457Cys Uncertain significance ★ ⚠ same type
ERI2 p.Ala102Ser Uncertain significance ★ ⚠ same type
ERI2 p.Ala19Val 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/eri2-p-arg572his (accessed [today's date]).

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