Is ERBIN p.Thr197= (c.591G>A) pathogenic?

ERBIN p.Thr197= (c.591G>A) is classified Likely benign in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-02). Ultra-rare (popmax 0.017%, nfe).

How common is ERBIN p.Thr197= (c.591G>A) in the general population?

ERBIN p.Thr197= (c.591G>A) is ultra-rare (popmax 0.017%, nfe) (gnomAD).

ERBIN p.Thr197=

c.591G>A · rs146514222 · VCV2730326

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.6, phastCons 1
Overall
CADD	11.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% European (non-Finnish) · 199/1,169,262 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0128% 205/1,598,796 alleles · ultra-rare exomes 201/1,446,782 · genomes 4/152,014 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.017%	5,876
Remaining individualsnot grpmax-eligible	0.00646%	15,474
Finnishnot grpmax-eligible	0.00157%	63,820
South Asian	0.00111%	89,878

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: ERBIN
Protein: p.Thr197=
Coding: c.591G>A
MANE Select: NM_001253697
dbSNP: rs146514222
Type: single nucleotide variant
Location: chr5:66021379 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB

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

Similar variants

ERBIN p.Thr197Ala Uncertain significance ★ ⚠ same residue
ERBIN p.Thr197Met Uncertain significance ★ ⚠ same residue
ERBIN p.Ala942Val Uncertain significance ★★ ⚠ same type
ERBIN p.Arg1096Gln Uncertain significance ★★ ⚠ same type
ERBIN p.Arg1166Gln Uncertain significance ★★ ⚠ same type
ERBIN p.Asn1035Ser Uncertain significance ★★ ⚠ same type
ERBIN p.Asn650Ser Uncertain significance ★★ ⚠ same type
ERBIN p.Asp530Tyr 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/erbin-p-thr197 (accessed [today's date]).

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