Is LCA5L p.Pro384Arg (c.1151C>G) pathogenic?

LCA5L p.Pro384Arg (c.1151C>G) is classified Uncertain significance in LCA5L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely benign (0.0982); Ultra-rare (popmax 0.0415%, nfe).

How common is LCA5L p.Pro384Arg (c.1151C>G) in the general population?

LCA5L p.Pro384Arg (c.1151C>G) is ultra-rare (popmax 0.0415%, nfe) (gnomAD).

What do computational predictors say about LCA5L p.Pro384Arg (c.1151C>G)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

LCA5L p.Pro384Arg

c.1151C>G · rs138657594 · VCV2345749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0415%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP -3, phastCons 0.14
Regional constraint	o/e 0.88	unconstrained · MANE · 23 kb · p 0.00069 · regional, not allelic
Overall
CADD	7.355	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0415% European (non-Finnish) · 487/1,173,886 alleles

Filtering AF 0.0384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0372%

Overall 0.0315% 506/1,603,816 alleles · ultra-rare exomes 486/1,451,642 · genomes 20/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0415%	2,410
Remaining individualsnot grpmax-eligible	0.0161%	6,216
Finnishnot grpmax-eligible	0.00626%	15,976
African / African-American	0.00536%	18,644
Admixed American	0.0017%	58,754

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: LCA5L
Protein: p.Pro384Arg
Coding: c.1151C>G
MANE Select: NM_152505
dbSNP: rs138657594
Type: single nucleotide variant
Location: chr21:39410277 (GRCh38)

Full LCA5L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/lca5l-p-pro384arg (accessed [today's date]).

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