Is ERBIN p.Ser660del (c.1975TCT[1]) pathogenic?

ERBIN p.Ser660del (c.1975TCT[1]) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-11). Very rare (popmax 0.00271%, afr).

How common is ERBIN p.Ser660del (c.1975TCT[1]) in the general population?

ERBIN p.Ser660del (c.1975TCT[1]) is very rare (popmax 0.00271%, afr) (gnomAD).

ERBIN p.Ser660del

c.1975TCT[1] · rs776881957 · VCV1514823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 6.3, phastCons 1
Overall
CADD	19.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% African / African-American · 2/73,726 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00219% 35/1,601,712 alleles · very rare exomes 30/1,450,300 · genomes 5/151,412 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00323%	30,996
African / African-Americangrpmax	0.00271%	36,863
European (non-Finnish)	0.00255%	39,184
Finnishnot grpmax-eligible	0.00157%	63,752

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser660del
Coding: c.1975TCT[1]
MANE Select: NM_001253697
dbSNP: rs776881957
Type: Microsatellite
Location: chr5:66050853 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 56.01 · 11 PDB
Residue 660: the 'disordered' region

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

Similar variants

ERBIN p.Ser660= Likely benign ★ same residue
ERBIN p.Ile958del Uncertain significance ★ same type
ERBIN p.Pro1118del Uncertain significance ★ same type
ERBIN c.1021-7_1021-6del Likely benign ★ same type
ERBIN c.1428+17_1428+23del Likely benign ★ 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-ser660del (accessed [today's date]).

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