Is FANCF p.Ala186Val (c.557C>T) pathogenic?

FANCF p.Ala186Val (c.557C>T) is classified Benign/Likely benign in FANCF (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0979); Low-frequency (popmax 2.03%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with FANCF p.Ala186Val (c.557C>T)?

FANCF p.Ala186Val (c.557C>T) is associated with hereditary neoplastic syndrome, breast cancer, ovarian cancer (ClinVar).

How common is FANCF p.Ala186Val (c.557C>T) in the general population?

FANCF p.Ala186Val (c.557C>T) is low-frequency (popmax 2.03%, mid) (gnomAD).

What do computational predictors say about FANCF p.Ala186Val (c.557C>T)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

FANCF p.Ala186Val

c.557C>T · rs113910234 · VCV134349

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.53	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 0.11	GERP -2.2, phastCons 0.002
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	9.216	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 2.03% Middle Eastern · 123/6,062 alleles

Filtering AF 1.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.63%

Overall 0.852% 13,756/1,614,164 alleles · low-frequency exomes 12,804/1,461,790 · genomes 952/152,374 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.03%	49
South Asian	1.66%	60
European (non-Finnish)	0.91%	110
Remaining individualsnot grpmax-eligible	0.851%	118
Finnishnot grpmax-eligible	0.532%	188
Admixed American	0.485%	206
Ashkenazi Jewishnot grpmax-eligible	0.402%	249
African / African-American	0.128%	782
East Asian	0.00446%	22,439

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.Ala186Val
Coding: c.557C>T
MANE Select: NM_022725
dbSNP: rs113910234
Type: single nucleotide variant
Location: chr11:22625254 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 186: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast cancer ovarian cancer 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-ala186val (accessed [today's date]).

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