Is ECI2 p.Arg12Gln (c.35G>A) pathogenic?

ECI2 p.Arg12Gln (c.35G>A) is classified Likely benign in ECI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely benign (0.2113); Very rare (popmax 0.00409%, nfe).

How common is ECI2 p.Arg12Gln (c.35G>A) in the general population?

ECI2 p.Arg12Gln (c.35G>A) is very rare (popmax 0.00409%, nfe) (gnomAD).

What do computational predictors say about ECI2 p.Arg12Gln (c.35G>A)?

AlphaMissense predicts likely benign (score 0.2113) — an in-silico prediction, not a clinical call.

ECI2 p.Arg12Gln

c.35G>A · rs754622931 · VCV2509001

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00409%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2113	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -7.35	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 -0.73	GERP -2.7
Regional constraint	o/e 0.99	unconstrained · MANE · 20 kb · p 0.84 · regional, not allelic
Overall
CADD	12.46	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 0.00409% European (non-Finnish) · 48/1,172,740 alleles

Filtering AF 0.00317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0028%

Overall 0.00306% 49/1,600,976 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00409%	24,432
Remaining individualsnot grpmax-eligible	0.00162%	61,706

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: ECI2
Protein: p.Arg12Gln
Coding: c.35G>A
MANE Select: NM_206836
dbSNP: rs754622931
Type: single nucleotide variant
Location: chr6:4135526 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.40 · 5 PDB

Full ECI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECI2 p.Ala11Pro Uncertain significance ★ ⚠ same type
ECI2 p.Ala67Thr Uncertain significance ★ ⚠ same type
ECI2 p.Ala67Val Uncertain significance ★ ⚠ same type
ECI2 p.Ala7Val Uncertain significance ★ ⚠ same type
ECI2 p.Ala95Thr Uncertain significance ★ ⚠ same type
ECI2 p.Arg157Trp Uncertain significance ★ same type
ECI2 p.Cys15Tyr Uncertain significance ★ ⚠ same type
ECI2 p.Glu147Lys 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/eci2-p-arg12gln (accessed [today's date]).

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