Is CFAP91 p.Ala718Thr (c.2152G>A) pathogenic?

CFAP91 p.Ala718Thr (c.2152G>A) is classified Uncertain significance in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.0818); Ultra-rare (popmax 0.02%, eas).

How common is CFAP91 p.Ala718Thr (c.2152G>A) in the general population?

CFAP91 p.Ala718Thr (c.2152G>A) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about CFAP91 p.Ala718Thr (c.2152G>A)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

CFAP91 p.Ala718Thr

c.2152G>A · rs896679701 · VCV3143708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 0.73, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 48 kb · p 0.55 · regional, not allelic
Overall
CADD	19.19	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% East Asian · 9/44,900 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00124% 20/1,613,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,989
African / African-American	0.00401%	24,966
South Asian	0.0011%	91,084
European (non-Finnish)	0.000593%	168,545

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: CFAP91
Protein: p.Ala718Thr
Coding: c.2152G>A
MANE Select: NM_033364
dbSNP: rs896679701
Type: single nucleotide variant
Location: chr3:119750945 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.20 · 1 PDB

Full CFAP91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP91 c.359+1G>A Likely pathogenic ★ same type
CFAP91 p.Gln545Ter Likely pathogenic ★ same type
CFAP91 c.501-3T>C Uncertain significance ★ same type
CFAP91 p.Ala249Asp Uncertain significance ★ ⚠ same type
CFAP91 p.Ala256Thr Uncertain significance ★ ⚠ same type
CFAP91 p.Ala449Val Uncertain significance ★ ⚠ same type
CFAP91 p.Ala598Ser Uncertain significance ★ ⚠ same type
CFAP91 p.Arg102Trp 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/cfap91-p-ala718thr (accessed [today's date]).

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