Is CFAP77 p.Pro71Leu (c.212C>T) pathogenic?

CFAP77 p.Pro71Leu (c.212C>T) is classified Uncertain significance in CFAP77 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: ambiguous (0.3439); Very rare (popmax 0.00119%, nfe).

How common is CFAP77 p.Pro71Leu (c.212C>T) in the general population?

CFAP77 p.Pro71Leu (c.212C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about CFAP77 p.Pro71Leu (c.212C>T)?

AlphaMissense predicts ambiguous (score 0.3439) — an in-silico prediction, not a clinical call.

CFAP77 p.Pro71Leu

c.212C>T · VCV4652979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3439	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -9.88	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 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 162 kb · p 0.31 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P107L vs ClinVar P71L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,178,908 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000869% 14/1,611,712 alleles · very rare

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: CFAP77
Protein: p.Pro71Leu
Coding: c.212C>T
MANE Select: NM_001282957
Type: single nucleotide variant
Location: chr9:132498711 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 2 PDB

Full CFAP77 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP77 c.196-16283C>G Uncertain significance ★ ⚠ same type
CFAP77 c.196-16315C>T Uncertain significance ★ ⚠ same type
CFAP77 c.196-16327A>G Uncertain significance ★ ⚠ same type
CFAP77 c.196-16333C>T Uncertain significance ★ ⚠ same type
CFAP77 c.196-16357C>T Uncertain significance ★ ⚠ same type
CFAP77 p.Ala127Val Uncertain significance ★ ⚠ same type
CFAP77 p.Ala256Val Uncertain significance ★ ⚠ same type
CFAP77 p.Arg118Gln 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/cfap77-p-pro71leu (accessed [today's date]).

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