Is CFAP100 p.Ser362Leu (c.1085C>T) pathogenic?

CFAP100 p.Ser362Leu (c.1085C>T) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0117%, amr).

How common is CFAP100 p.Ser362Leu (c.1085C>T) in the general population?

CFAP100 p.Ser362Leu (c.1085C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CFAP100 p.Ser362Leu (c.1085C>T)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

CFAP100 p.Ser362Leu

c.1085C>T · rs866705267 · VCV3143287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.94	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 1.6	GERP 1.6, phastCons 0.91
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	22.7	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 0.0117% Admixed American · 7/59,880 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000868% 14/1,612,800 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,554
Remaining individualsnot grpmax-eligible	0.0032%	31,211
Finnishnot grpmax-eligible	0.00313%	31,944
European (non-Finnish)	0.000254%	393,153

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: CFAP100
Protein: p.Ser362Leu
Coding: c.1085C>T
MANE Select: NM_182628
dbSNP: rs866705267
Type: single nucleotide variant
Location: chr3:126423327 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85 · 1 PDB
Residue 362: the 'disordered' region

Full CFAP100 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP100 p.Ser362Trp Uncertain significance ★ ⚠ same residue
CFAP100 p.Ala126Ser Uncertain significance ★ ⚠ same type
CFAP100 p.Ala179Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala224Asp Uncertain significance ★ ⚠ same type
CFAP100 p.Ala499Thr Uncertain significance ★ ⚠ same type
CFAP100 p.Ala563Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala565Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala73Pro 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/cfap100-p-ser362leu (accessed [today's date]).

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