Is CEP85L p.Ala7Val (c.20C>T) pathogenic?

CEP85L p.Ala7Val (c.20C>T) is classified Benign in CEP85L (ClinVar, Single submitter, 2 submitters; last evaluated 2022-06-17). AlphaMissense: ambiguous (0.4145); Rare (popmax 0.542%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP85L p.Ala7Val (c.20C>T)?

CEP85L p.Ala7Val (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP85L p.Ala7Val (c.20C>T) in the general population?

CEP85L p.Ala7Val (c.20C>T) is rare (popmax 0.542%, amr) (gnomAD).

What do computational predictors say about CEP85L p.Ala7Val (c.20C>T)?

AlphaMissense predicts ambiguous (score 0.4145) — an in-silico prediction, not a clinical call.

CEP85L p.Ala7Val

c.20C>T · rs187158499 · VCV2212915

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4145 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.542%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4145	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.63, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 19 kb · p 0.51 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.542% Admixed American · 249/45,936 alleles

Filtering AF 0.487% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.465%

Overall 0.017% 253/1,492,186 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.542%	184
Remaining individualsnot grpmax-eligible	0.00517%	19,328
European (non-Finnish)	8.88e-05%	1,126,616

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_001042475
dbSNP: rs187158499
Type: single nucleotide variant
Location: chr6:118651250 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.98
Residue 7: the 'disordered' region

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.Arg241Ser 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

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-ala7val (accessed [today's date]).

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