Is IMPG1 p.Leu613Pro (c.1838T>C) pathogenic?

IMPG1 p.Leu613Pro (c.1838T>C) is classified Uncertain significance in IMPG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-09-10). AlphaMissense: likely pathogenic (0.9851); Absent from gnomAD v4.1; Associated with benign concentric annular macular dystrophy.

What condition is associated with IMPG1 p.Leu613Pro (c.1838T>C)?

IMPG1 p.Leu613Pro (c.1838T>C) is associated with benign concentric annular macular dystrophy (ClinVar).

How common is IMPG1 p.Leu613Pro (c.1838T>C) in the general population?

IMPG1 p.Leu613Pro (c.1838T>C) is absent from gnomAD v4.1 (gnomAD).

How is Benign concentric annular macular dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IMPG1 p.Leu613Pro (c.1838T>C)?

AlphaMissense predicts likely pathogenic (score 0.9851) — an in-silico prediction, not a clinical call.

IMPG1 p.Leu613Pro

c.1838T>C · rs1781948884 · VCV1043806

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

benign concentric annular macular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9851	likely pathogenic · top 1% in IMPG1
REVEL	0.631	indeterminate
SaProt	LLR -18.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 29 kb · p 0.44 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IMPG1
Protein: p.Leu613Pro
Coding: c.1838T>C
MANE Select: NM_001563
dbSNP: rs1781948884
Type: single nucleotide variant
Location: chr6:75947520 (GRCh38)
Gene constraint: LOEUF 1.217 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.26
Residue 613: a UniProt-annotated variant site (in rp91; uncertain significance); the sea 2 domain

Full IMPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

benign concentric annular macular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Benign concentric annular macular dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

IMPG1 p.Leu613Val Uncertain significance ★ same residue
IMPG1 c.1824+1G>A Pathogenic/Likely pathogenic ★★ same condition
IMPG1 p.Pro410Thr Uncertain significance ★★ ⚠ same condition
IMPG1 p.His518Asp Benign ★★ same condition
IMPG1 p.Leu579Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
IMPG1 p.Leu626Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
IMPG1 p.Phe620Leu Uncertain significance ★ ⚠ same condition
IMPG1 p.Ser360Asn Uncertain significance ★ ⚠ 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/impg1-p-leu613pro (accessed [today's date]).

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