Is CFAP43 p.Ser991Ala (c.2971T>G) pathogenic?

CFAP43 p.Ser991Ala (c.2971T>G) is classified Benign in CFAP43 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0783); Rare (popmax 0.493%, eas).

How common is CFAP43 p.Ser991Ala (c.2971T>G) in the general population?

CFAP43 p.Ser991Ala (c.2971T>G) is rare (popmax 0.493%, eas) (gnomAD).

What do computational predictors say about CFAP43 p.Ser991Ala (c.2971T>G)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

CFAP43 p.Ser991Ala

c.2971T>G · rs138801737 · VCV708370

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.493%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.54	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 4.4	GERP 0.84, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.0013 · regional, not allelic
Overall
CADD	22.3	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 0.493% East Asian · 221/44,872 alleles

Filtering AF 0.439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.419%

Overall 0.0833% 1,345/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.917%	109
East Asiangrpmax	0.493%	203
Ashkenazi Jewishnot grpmax-eligible	0.111%	897
Remaining individualsnot grpmax-eligible	0.109%	919
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.0338%	2,957
South Asian	0.0329%	3,036
Admixed American	0.00167%	60,016
African / African-American	0.00133%	75,052

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP43
Protein: p.Ser991Ala
Coding: c.2971T>G
MANE Select: NM_025145
dbSNP: rs138801737
Type: single nucleotide variant
Location: chr10:104166556 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 1 PDB
Residue 991: a UniProt-annotated variant site (in spgf19)

Full CFAP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP43 p.Arg894Ter Pathogenic/Likely pathogenic ★★ same type
CFAP43 p.Thr1075Lys Uncertain significance ★★ ⚠ same type
CFAP43 c.2142-4A>G Benign ★★ same type
CFAP43 p.Glu1540Gly Benign/Likely benign ★★ same type
CFAP43 p.Leu1542Val Benign/Likely benign ★★ same type
CFAP43 p.Leu616Phe Benign ★★ ⚠ same type
CFAP43 p.Leu802= Benign ★★ same type
CFAP43 p.Pro246= 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/cfap43-p-ser991ala (accessed [today's date]).

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