Is LCA5 p.Val39Phe (c.115G>T) pathogenic?

LCA5 p.Val39Phe (c.115G>T) is classified Uncertain significance in LCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0975); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LCA5 p.Val39Phe (c.115G>T)?

LCA5 p.Val39Phe (c.115G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LCA5 p.Val39Phe (c.115G>T) in the general population?

LCA5 p.Val39Phe (c.115G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LCA5 p.Val39Phe (c.115G>T)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

LCA5 p.Val39Phe

c.115G>T · rs2533451285 · VCV2335358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP -0.11
Regional constraint	o/e 1.02	unconstrained · MANE · 32 kb · p 0.58 · regional, not allelic
Overall
CADD	11.81	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

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: LCA5
Protein: p.Val39Phe
Coding: c.115G>T
MANE Select: NM_001122769
dbSNP: rs2533451285
Type: single nucleotide variant
Location: chr6:79518780 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.05
Residue 39: the 'disordered' region

Full LCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LCA5 p.Ala107Thr Uncertain significance ★★ ⚠ same condition
LCA5 p.Ala425Pro Uncertain significance ★★ ⚠ same condition
LCA5 p.Ala683Pro Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg163His Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg174His Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg183Gln Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg213Gly Uncertain significance ★★ ⚠ same condition
LCA5 p.Arg375Ser 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/lca5-p-val39phe (accessed [today's date]).

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