Is ERBIN p.Gln172Arg (c.515A>G) pathogenic?

ERBIN p.Gln172Arg (c.515A>G) is classified Uncertain significance in ERBIN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). AlphaMissense: ambiguous (0.3851); Very rare (popmax 0.00457%, amr).

How common is ERBIN p.Gln172Arg (c.515A>G) in the general population?

ERBIN p.Gln172Arg (c.515A>G) is very rare (popmax 0.00457%, amr) (gnomAD).

What do computational predictors say about ERBIN p.Gln172Arg (c.515A>G)?

AlphaMissense predicts ambiguous (score 0.3851) — an in-silico prediction, not a clinical call.

ERBIN p.Gln172Arg

c.515A>G · rs1231546642 · VCV1007529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00457%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3851	ambiguous
REVEL	0.252	benign-leaning
SaProt	LLR -6.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 6.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 56 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	26.0	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 0.00457% Admixed American · 2/43,786 alleles

Filtering AF 0.000757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000283%

Overall 0.000275% 4/1,453,174 alleles · very rare exomes 2/1,301,042 · genomes 2/152,132 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00457%	21,893
Ashkenazi Jewishnot grpmax-eligible	0.00372%	26,850
European (non-Finnish)	9.31e-05%	1,074,052

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.Gln172Arg
Coding: c.515A>G
MANE Select: NM_001253697
dbSNP: rs1231546642
Type: single nucleotide variant
Location: chr5:66014707 (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.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
ERBIN p.His521Arg 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-gln172arg (accessed [today's date]).

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