Is CAMSAP3 p.Phe684Ile (c.2050T>A) pathogenic?

CAMSAP3 p.Phe684Ile (c.2050T>A) is classified Uncertain significance in CAMSAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely pathogenic (0.8623); Rare (popmax 0.283%, nfe).

How common is CAMSAP3 p.Phe684Ile (c.2050T>A) in the general population?

CAMSAP3 p.Phe684Ile (c.2050T>A) is rare (popmax 0.283%, nfe) (gnomAD).

What do computational predictors say about CAMSAP3 p.Phe684Ile (c.2050T>A)?

AlphaMissense predicts likely pathogenic (score 0.8623) — an in-silico prediction, not a clinical call.

CAMSAP3 p.Phe684Ile

c.2050T>A · rs202045562 · VCV2341888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8623 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.283%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8623	likely pathogenic
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 6,687 bp · p 0.29 · regional, not allelic
Overall
CADD	21.4	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 0.283% European (non-Finnish) · 3,245/1,145,468 alleles

Filtering AF 0.275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.272%

Overall 0.234% 3,591/1,536,490 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.283%	353
Admixed American	0.253%	395
Remaining individualsnot grpmax-eligible	0.2%	499
Finnishnot grpmax-eligible	0.0901%	1,109
African / African-American	0.041%	2,439
South Asian	0.0286%	3,501
Middle Eastern	0.0168%	5,968

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: CAMSAP3
Protein: p.Phe684Ile
Coding: c.2050T>A
MANE Select: NM_020902
dbSNP: rs202045562
Type: single nucleotide variant
Location: chr19:7612543 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 60.70
Residue 684: the 'disordered' region

Full CAMSAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAMSAP3 p.Phe684Ser Uncertain significance ★ ⚠ same residue
CAMSAP3 p.Ala239= Benign ★★ same type
CAMSAP3 p.Arg931Gln Benign ★★ same type
CAMSAP3 p.Pro381= Benign ★★ same type
CAMSAP3 p.Tyr294= Benign ★★ same type
CAMSAP3 c.622-299A>G Uncertain significance ★ same type
CAMSAP3 p.Ala1002Val Uncertain significance ★ ⚠ same type
CAMSAP3 p.Ala1098Val Uncertain significance ★ ⚠ same type

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/camsap3-p-phe684ile (accessed [today's date]).

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