Is CFAP97 p.Ile44Thr (c.131T>C) pathogenic?

CFAP97 p.Ile44Thr (c.131T>C) is classified Uncertain significance in CFAP97 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). AlphaMissense: likely benign (0.0548); Ultra-rare (popmax 0.02%, nfe).

How common is CFAP97 p.Ile44Thr (c.131T>C) in the general population?

CFAP97 p.Ile44Thr (c.131T>C) is ultra-rare (popmax 0.02%, nfe) (gnomAD).

What do computational predictors say about CFAP97 p.Ile44Thr (c.131T>C)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

CFAP97 p.Ile44Thr

c.131T>C · rs371375696 · VCV2341072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -5.88	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 0.079	GERP 0.68
Regional constraint	o/e 1.06	unconstrained · MANE · 28 kb · p 0.14 · regional, not allelic
Overall
CADD	6.116	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 0.02% European (non-Finnish) · 236/1,179,696 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0156% 252/1,613,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.02%	4,999
Remaining individualsnot grpmax-eligible	0.0176%	5,677
Admixed American	0.00667%	14,993
Finnishnot grpmax-eligible	0.00157%	63,832

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.Ile44Thr
Coding: c.131T>C
MANE Select: NM_020827
dbSNP: rs371375696
Type: single nucleotide variant
Location: chr4:185191066 (GRCh38)
Gene constraint: LOEUF 1.095 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.55
Residue 44: the 'disordered' region

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

Similar variants

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
CFAP97 p.Arg479Trp 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-ile44thr (accessed [today's date]).

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