Is FANCF p.Ser191Arg (c.573C>G) pathogenic?

FANCF p.Ser191Arg (c.573C>G) is classified Conflicting classifications of pathogenicity in FANCF (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2024-11-05). AlphaMissense: likely benign (0.2228); Rare (popmax 0.247%, mid); Associated with Inborn genetic diseases.

What condition is associated with FANCF p.Ser191Arg (c.573C>G)?

FANCF p.Ser191Arg (c.573C>G) is associated with Inborn genetic diseases, Fanconi anemia complementation group F, Fanconi anemia (ClinVar).

How common is FANCF p.Ser191Arg (c.573C>G) in the general population?

FANCF p.Ser191Arg (c.573C>G) is rare (popmax 0.247%, mid) (gnomAD).

What do computational predictors say about FANCF p.Ser191Arg (c.573C>G)?

AlphaMissense predicts likely benign (score 0.2228) — an in-silico prediction, not a clinical call.

FANCF p.Ser191Arg

c.573C>G · rs146219377 · VCV456284

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2228 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.247%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2228	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.90	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 0.91	GERP 0.96, phastCons 0.32
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	6.56	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 0.247% Middle Eastern · 15/6,062 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00979% 158/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.247%	404
African / African-American	0.0706%	1,417
Admixed American	0.0383%	2,610
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.00549%	18,218
European (non-Finnish)	0.00339%	29,501

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: FANCF
Protein: p.Ser191Arg
Coding: c.573C>G
MANE Select: NM_022725
dbSNP: rs146219377
Type: single nucleotide variant
Location: chr11:22625238 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 191: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group F Fanconi anemia

Similar variants

FANCF p.Gln65Ter Likely pathogenic ★★ same condition
FANCF p.Glu220Ter Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Glu223Ter Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Met1Arg Pathogenic/Likely pathogenic ★★ same condition
FANCF c.-21A>G Uncertain significance ★★ same condition
FANCF c.-31T>C Uncertain significance ★★ same condition
FANCF c.*1879T>C Uncertain significance ★★ same condition
FANCF p.Ala124Ser Uncertain significance ★★ ⚠ same condition

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/fancf-p-ser191arg (accessed [today's date]).

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