Is CEP85L p.Arg241Ser (c.723A>C) pathogenic?

CEP85L p.Arg241Ser (c.723A>C) is classified Uncertain significance in CEP85L (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-29). AlphaMissense: likely benign (0.153); Ultra-rare (popmax 0.0549%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEP85L p.Arg241Ser (c.723A>C)?

CEP85L p.Arg241Ser (c.723A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP85L p.Arg241Ser (c.723A>C) in the general population?

CEP85L p.Arg241Ser (c.723A>C) is ultra-rare (popmax 0.0549%, sas) (gnomAD).

What do computational predictors say about CEP85L p.Arg241Ser (c.723A>C)?

AlphaMissense predicts likely benign (score 0.153) — an in-silico prediction, not a clinical call.

CEP85L p.Arg241Ser

c.723A>C · rs779389767 · VCV2230580

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.153 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.153	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -5.34	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 2.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 167 kb · p 0.12 · regional, not allelic
Overall
CADD	16.45	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 0.0549% South Asian · 50/91,090 alleles

Filtering AF 0.0427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0031% 50/1,613,996 alleles · ultra-rare

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: CEP85L
Protein: p.Arg241Ser
Coding: c.723A>C
MANE Select: NM_001042475
dbSNP: rs779389767
Type: single nucleotide variant
Location: chr6:118565826 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.98

Full CEP85L 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

CEP85L p.Arg151Gln Uncertain significance ★★ ⚠ same condition
CEP85L p.Gly122Ser Uncertain significance ★★ ⚠ same condition
CEP85L p.Ile186Val Uncertain significance ★★ ⚠ same condition
CEP85L p.Pro152Ala Uncertain significance ★★ ⚠ same condition
CEP85L p.Ser262Gly Uncertain significance ★★ ⚠ same condition
CEP85L p.Thr66Ile Uncertain significance ★★ ⚠ same condition
CEP85L p.Lys220Thr Likely benign ★★ same condition
CEP85L c.1020+6G>T 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/cep85l-p-arg241ser (accessed [today's date]).

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