Is CFAP92 p.Arg114His (c.341G>A) pathogenic?

CFAP92 p.Arg114His (c.341G>A) is classified Uncertain significance in CFAP92 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.1289); Very rare (popmax 0.00381%, nfe).

How common is CFAP92 p.Arg114His (c.341G>A) in the general population?

CFAP92 p.Arg114His (c.341G>A) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about CFAP92 p.Arg114His (c.341G>A)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

CFAP92 p.Arg114His

c.341G>A · rs375148155 · VCV2553600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -8.62	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 0.89	GERP 0.052, phastCons 0.43
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.026 · regional, not allelic
Overall
CADD	10.61	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 0.00381% European (non-Finnish) · 45/1,179,724 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00316% 51/1,613,618 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,216
South Asian	0.00329%	30,353
East Asian	0.00223%	44,860
Remaining individualsnot grpmax-eligible	0.0016%	62,464
African / African-American	0.00133%	74,916

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: CFAP92
Protein: p.Arg114His
Coding: c.341G>A
MANE Select: NM_001394090
dbSNP: rs375148155
Type: single nucleotide variant
Location: chr3:128988840 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.39

Full CFAP92 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP92 p.Arg114Cys Uncertain significance ★ ⚠ same residue
ACAD9 c.1692+1G>A Likely pathogenic ★★ same type
ACAD9 p.Arg532Gln Likely pathogenic ★★ ⚠ same type
ACAD9 p.Asn569His Uncertain significance ★★ ⚠ same type
ACAD9 p.Glu596Lys Uncertain significance ★★ ⚠ same type
ACAD9 c.1692+145G>C Benign ★★ same type
ACAD9 c.*26C>T Benign/Likely benign ★★ same type
ACAD9 c.*331T>G Benign/Likely benign ★★ 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/cfap92-p-arg114his (accessed [today's date]).

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