Is CAMSAP1 p.Phe1075Leu (c.3225C>A) pathogenic?

CAMSAP1 p.Phe1075Leu (c.3225C>A) is classified Uncertain significance in CAMSAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: ambiguous (0.5087); Very rare (popmax 0.00878%, sas); Associated with Inborn genetic diseases.

What condition is associated with CAMSAP1 p.Phe1075Leu (c.3225C>A)?

CAMSAP1 p.Phe1075Leu (c.3225C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CAMSAP1 p.Phe1075Leu (c.3225C>A) in the general population?

CAMSAP1 p.Phe1075Leu (c.3225C>A) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about CAMSAP1 p.Phe1075Leu (c.3225C>A)?

AlphaMissense predicts ambiguous (score 0.5087) — an in-silico prediction, not a clinical call.

CAMSAP1 p.Phe1075Leu

c.3225C>A · rs573187485 · VCV3136851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5087	ambiguous
REVEL	0.129	moderately benign-leaning
SaProt	LLR -5.11	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 -8.6	GERP -3.2
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.41 · regional, not allelic
Overall
CADD	0.004	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 0.00878% South Asian · 8/91,086 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00105% 17/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
South Asiangrpmax	0.00878%	11,386
African / African-American	0.004%	25,026
Admixed American	0.00167%	60,028
European (non-Finnish)	0.00017%	589,950

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CAMSAP1
Protein: p.Phe1075Leu
Coding: c.3225C>A
MANE Select: NM_015447
dbSNP: rs573187485
Type: single nucleotide variant
Location: chr9:135821436 (GRCh38)
Gene constraint: LOEUF 0.544 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.21 · 4 PDB
Residue 1075: a UniProt-annotated variant site (in cdcbm12); the 'disordered' region

Full CAMSAP1 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

CAMSAP1 p.Leu29Met Uncertain significance ★★ ⚠ same condition
CAMSAP1 c.4387+6G>A Uncertain significance ★ same condition
CAMSAP1 p.Ala1105Val Uncertain significance ★ ⚠ same condition
CAMSAP1 p.Ala1243Val Uncertain significance ★ ⚠ same condition
CAMSAP1 p.Ala1323Val Uncertain significance ★ ⚠ same condition
CAMSAP1 p.Ala1405Thr Uncertain significance ★ ⚠ same condition
CAMSAP1 p.Ala1405Val Uncertain significance ★ ⚠ same condition
CAMSAP1 p.Ala1452Gly 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/camsap1-p-phe1075leu (accessed [today's date]).

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