Is ERC2 p.Arg609Gln (c.1826G>A) pathogenic?

ERC2 p.Arg609Gln (c.1826G>A) is classified Uncertain significance in ERC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1074); Ultra-rare (popmax 0.0767%, amr).

How common is ERC2 p.Arg609Gln (c.1826G>A) in the general population?

ERC2 p.Arg609Gln (c.1826G>A) is ultra-rare (popmax 0.0767%, amr) (gnomAD).

What do computational predictors say about ERC2 p.Arg609Gln (c.1826G>A)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

ERC2 p.Arg609Gln

c.1826G>A · rs371352737 · VCV3090094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0767%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.658	pathogenic-leaning
SaProt	LLR -7.69	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 7.2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 132 kb · p 3.7e-11 · regional, not allelic
Overall
CADD	32.0	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 0.0767% Admixed American · 46/59,986 alleles

Filtering AF 0.0591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0528%

Overall 0.00508% 82/1,613,514 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0767%	1,304
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,917
Remaining individualsnot grpmax-eligible	0.0144%	6,941
South Asian	0.00769%	13,007
African / African-American	0.00267%	37,511
East Asian	0.00223%	44,850
European (non-Finnish)	0.00102%	98,307

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: ERC2
Protein: p.Arg609Gln
Coding: c.1826G>A
MANE Select: NM_015576
dbSNP: rs371352737
Type: single nucleotide variant
Location: chr3:56010543 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 74.26

Full ERC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERC2 p.Arg609Trp Uncertain significance ★ ⚠ same residue
ERC2 p.Ala105Ser Uncertain significance ★ ⚠ same type
ERC2 p.Ala107Thr Uncertain significance ★ ⚠ same type
ERC2 p.Ala202Val Uncertain significance ★ ⚠ same type
ERC2 p.Ala251Val Uncertain significance ★ ⚠ same type
ERC2 p.Ala333Ser Uncertain significance ★ ⚠ same type
ERC2 p.Ala371Pro Uncertain significance ★ ⚠ same type
ERC2 p.Ala724Thr 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/erc2-p-arg609gln (accessed [today's date]).

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