Is FANCF p.Arg138Ser (c.412C>A) pathogenic?

FANCF p.Arg138Ser (c.412C>A) is classified Conflicting classifications of pathogenicity in FANCF (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-10). AlphaMissense: likely pathogenic (0.6983); Rare (popmax 0.152%, sas); Associated with Fanconi anemia.

What condition is associated with FANCF p.Arg138Ser (c.412C>A)?

FANCF p.Arg138Ser (c.412C>A) is associated with Fanconi anemia, Fanconi anemia complementation group F (ClinVar).

How common is FANCF p.Arg138Ser (c.412C>A) in the general population?

FANCF p.Arg138Ser (c.412C>A) is rare (popmax 0.152%, sas) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FANCF p.Arg138Ser (c.412C>A)?

AlphaMissense predicts likely pathogenic (score 0.6983) — an in-silico prediction, not a clinical call.

FANCF p.Arg138Ser

c.412C>A · rs565372884 · VCV701972

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6983 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.152%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.6983	likely pathogenic
REVEL	0.244	benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	23.3	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 0.152% South Asian · 138/91,088 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00991% 160/1,614,192 alleles · rare exomes 149/1,461,836 · genomes 11/152,356 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.152%	660
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Middle Eastern	0.0165%	6,062
African / African-American	0.00133%	75,082
European (non-Finnish)	0.000508%	196,673

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.Arg138Ser
Coding: c.412C>A
MANE Select: NM_022725
dbSNP: rs565372884
Type: single nucleotide variant
Location: chr11:22625399 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 138: an α-helix

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

Disease context

Fanconi anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group F

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCF p.Arg138_Arg139insLeuAlaArg Uncertain significance ★ same residue
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

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-arg138ser (accessed [today's date]).

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