Is ERBIN p.Leu352Phe (c.1054C>T) pathogenic?

ERBIN p.Leu352Phe (c.1054C>T) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-26). AlphaMissense: likely pathogenic (0.8804); Very rare (popmax 0.00355%, amr).

How common is ERBIN p.Leu352Phe (c.1054C>T) in the general population?

ERBIN p.Leu352Phe (c.1054C>T) is very rare (popmax 0.00355%, amr) (gnomAD).

What do computational predictors say about ERBIN p.Leu352Phe (c.1054C>T)?

AlphaMissense predicts likely pathogenic (score 0.8804) — an in-silico prediction, not a clinical call.

ERBIN p.Leu352Phe

c.1054C>T · rs866023448 · VCV1944572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00355%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8804	likely pathogenic
REVEL	0.688	pathogenic-leaning
SaProt	LLR -12.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 6.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00355% Admixed American · 2/56,392 alleles

Filtering AF 0.000588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00022%

Overall 0.000314% 5/1,594,178 alleles · very rare exomes 2/1,442,354 · genomes 3/151,824 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00355%	28,196
African / African-American	0.00273%	36,687
Remaining individualsnot grpmax-eligible	0.00162%	61,572

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.Leu352Phe
Coding: c.1054C>T
MANE Select: NM_001253697
dbSNP: rs866023448
Type: single nucleotide variant
Location: chr5:66026335 (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.Leu352= Likely benign ★ 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
ERBIN p.Cys658Ser 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-leu352phe (accessed [today's date]).

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