Is CFAP70 p.Leu1049Phe (c.3145C>T) pathogenic?

CFAP70 p.Leu1049Phe (c.3145C>T) is classified Uncertain significance in CFAP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). AlphaMissense: likely benign (0.1121); Very rare (popmax 0.0011%, sas).

How common is CFAP70 p.Leu1049Phe (c.3145C>T) in the general population?

CFAP70 p.Leu1049Phe (c.3145C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CFAP70 p.Leu1049Phe (c.3145C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

CFAP70 p.Leu1049Phe

c.3145C>T · VCV3832410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.67	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 1.9	GERP 0.22, phastCons 1
Overall
CADD	20.3	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 0.0011% South Asian · 1/90,992 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,458,176 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,992
European (non-Finnish)	0.00017%	588,575

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.Leu1049Phe
Coding: c.3145C>T
MANE Select: NM_001367801
Type: single nucleotide variant
Location: chr10:73269706 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.55
Residue 1049: a UniProt-annotated variant site (in spgf41; likely pathogenic)

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-leu1049phe (accessed [today's date]).

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