Is CFAP70 p.Pro499Ser (c.1495C>T) pathogenic?

CFAP70 p.Pro499Ser (c.1495C>T) is classified Uncertain significance in CFAP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.1073); Ultra-rare (popmax 0.0167%, nfe).

How common is CFAP70 p.Pro499Ser (c.1495C>T) in the general population?

CFAP70 p.Pro499Ser (c.1495C>T) is ultra-rare (popmax 0.0167%, nfe) (gnomAD).

What do computational predictors say about CFAP70 p.Pro499Ser (c.1495C>T)?

AlphaMissense predicts likely benign (score 0.1073) — an in-silico prediction, not a clinical call.

CFAP70 p.Pro499Ser

c.1495C>T · rs774844005 · VCV2382724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1073	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -6.30	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 5.6	GERP 2.8, phastCons 1
Overall
CADD	21.1	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 0.0167% European (non-Finnish) · 197/1,179,444 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.0127% 205/1,612,978 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0167%	5,987
Admixed American	0.00501%	19,978
Remaining individualsnot grpmax-eligible	0.00481%	20,807
African / African-American	0.00267%	37,431

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: CFAP70
Protein: p.Pro499Ser
Coding: c.1495C>T
MANE Select: NM_001367801
dbSNP: rs774844005
Type: single nucleotide variant
Location: chr10:73299637 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.55

Full CFAP70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP70 p.His372Tyr Likely benign ★★ same type
CFAP70 p.Ala433Pro Uncertain significance ★ ⚠ same type
CFAP70 p.Ala759Glu Uncertain significance ★ ⚠ same type
CFAP70 p.Ala78Thr Uncertain significance ★ ⚠ same type
CFAP70 p.Ala7Pro Uncertain significance ★ ⚠ same type
CFAP70 p.Ala948Val Uncertain significance ★ ⚠ same type
CFAP70 p.Ala955Ser Uncertain significance ★ ⚠ same type
CFAP70 p.Arg1045Trp 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/cfap70-p-pro499ser (accessed [today's date]).

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