Is CFAP97 p.His335Pro (c.1004A>C) pathogenic?

CFAP97 p.His335Pro (c.1004A>C) is classified Uncertain significance in CFAP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.101); Rare (popmax 0.819%, afr).

How common is CFAP97 p.His335Pro (c.1004A>C) in the general population?

CFAP97 p.His335Pro (c.1004A>C) is rare (popmax 0.819%, afr) (gnomAD).

What do computational predictors say about CFAP97 p.His335Pro (c.1004A>C)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

CFAP97 p.His335Pro

c.1004A>C · VCV4227247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.819%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -12.85	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.2, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 28 kb · p 0.14 · regional, not allelic
Overall
CADD	4.601	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 0.819% African / African-American · 610/74,466 alleles

Filtering AF 0.765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.744%

Overall 0.0424% 681/1,606,198 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.819%	122
Admixed American	0.0597%	1,674
Remaining individualsnot grpmax-eligible	0.0531%	1,884
South Asian	0.00112%	88,970
European (non-Finnish)	0.00017%	588,474

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: CFAP97
Protein: p.His335Pro
Coding: c.1004A>C
MANE Select: NM_020827
Type: single nucleotide variant
Location: chr4:185190193 (GRCh38)
Gene constraint: LOEUF 1.095 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.55

Full CFAP97 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP97 p.His335Tyr Likely benign ★ same residue
CFAP97 p.Glu383= Benign ★★ same type
CFAP97 p.Thr499Met Benign ★★ same type
CFAP97 p.Ala152Gly Uncertain significance ★ ⚠ same type
CFAP97 p.Ala448Thr Uncertain significance ★ ⚠ same type
CFAP97 p.Arg381Ser Uncertain significance ★ ⚠ same type
CFAP97 p.Arg389Gln Uncertain significance ★ ⚠ same type
CFAP97 p.Arg457His 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/cfap97-p-his335pro (accessed [today's date]).

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