Is ERI1 p.Leu16Pro (c.47T>C) pathogenic?

ERI1 p.Leu16Pro (c.47T>C) is classified Benign in ERI1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-16). AlphaMissense: likely benign (0.0417); Common (popmax 90.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with ERI1-related disorder.

What condition is associated with ERI1 p.Leu16Pro (c.47T>C)?

ERI1 p.Leu16Pro (c.47T>C) is associated with ERI1-related disorder (ClinVar).

What do computational predictors say about ERI1 p.Leu16Pro (c.47T>C)?

AlphaMissense predicts likely benign (score 0.0417) — an in-silico prediction, not a clinical call.

ERI1 p.Leu16Pro

Q: How common is ERI1 p.Leu16Pro (c.47T>C) in the general population?

ERI1 p.Leu16Pro (c.47T>C) is common (popmax 90.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.47T>C · rs2288672 · VCV3060400

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0417 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 90.7%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ERI1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0417	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -4.80	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 0.099	GERP -2, phastCons 0.006
Regional constraint	o/e 1.39	unconstrained · MANE · 27 kb · p 9.3e-16 · regional, not allelic
Overall
CADD	8.59	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 90.7% European (non-Finnish) · 897,630/989,524 alleles

Filtering AF 90.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 90.5%

Overall 89.6% 1,116,946/1,246,258 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	90.7%	1
Ashkenazi Jewishnot grpmax-eligible	90.3%	1
Finnishnot grpmax-eligible	89%	1
Amishnot grpmax-eligible	88.9%	1
Admixed American	88.9%	1
Remaining individualsnot grpmax-eligible	88.4%	1
South Asian	88.2%	1
Middle Eastern	86.4%	1
African / African-American	81.3%	1
East Asian	77%	1

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: ERI1
Protein: p.Leu16Pro
Coding: c.47T>C
MANE Select: NM_153332
dbSNP: rs2288672
Type: single nucleotide variant
Location: chr8:9003110 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 16: a UniProt-annotated variant site (in); the 'disordered' region

Full ERI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ERI1-related disorder

Similar variants

ERI1 p.Gln244Ter Likely pathogenic ★ same condition
ERI1 p.Lys237Asn Uncertain significance ★ ⚠ same condition
ERI1 c.582+10C>T Likely benign same condition
ERI1 c.583-9T>C Likely benign same condition
ERI1 p.Cys139= Likely benign same condition
ERI1 p.Pro24Arg Likely benign same condition
ERI1 p.Tyr109= Likely benign same condition
ERI1 c.109-11_109-6del Likely benign same condition

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/eri1-p-leu16pro (accessed [today's date]).

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