Is AIPL1 p.Ser78= (c.234C>T) pathogenic?

AIPL1 p.Ser78= (c.234C>T) is classified Conflicting classifications of pathogenicity in AIPL1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-07). Rare (popmax 0.397%, afr); Associated with Leber congenital amaurosis 4.

What condition is associated with AIPL1 p.Ser78= (c.234C>T)?

AIPL1 p.Ser78= (c.234C>T) is associated with Leber congenital amaurosis 4, retinitis pigmentosa (ClinVar).

How common is AIPL1 p.Ser78= (c.234C>T) in the general population?

AIPL1 p.Ser78= (c.234C>T) is rare (popmax 0.397%, afr) (gnomAD).

How is Cone rod dystrophy inherited?

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

AIPL1 p.Ser78=

c.234C>T · rs62635774 · VCV99791

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.397%, afr)

Conditions

Leber congenital amaurosis 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.8, phastCons 1
Overall
CADD	7.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.397% African / African-American · 297/74,834 alleles

Filtering AF 0.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.345%

Overall 0.0266% 429/1,613,838 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.397%	252
Middle Eastern	0.248%	404
Remaining individualsnot grpmax-eligible	0.0864%	1,157
Admixed American	0.0183%	5,455
South Asian	0.00439%	22,767
European (non-Finnish)	0.00407%	24,583

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: AIPL1
Protein: p.Ser78=
Coding: c.234C>T
MANE Select: NM_014336
dbSNP: rs62635774
Type: single nucleotide variant
Location: chr17:6433961 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 78: the ppiase fkbp-type domain

Full AIPL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

AIPL1 c.276+1G>A Pathogenic ★★★ same condition
AIPL1 c.277-2A>G Pathogenic ★★★ same condition
AIPL1 p.Ala197Pro Pathogenic ★★★ same condition
AIPL1 p.Arg270His Pathogenic ★★★ same condition
AIPL1 p.Arg32Ter Pathogenic ★★★ same condition
AIPL1 p.Asp51Gly Likely pathogenic ★★★ same condition
AIPL1 p.Cys239Arg Likely pathogenic ★★★ same condition
AIPL1 p.Cys89Arg Pathogenic ★★★ 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/aipl1-p-ser78 (accessed [today's date]).

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