Is FANCL p.Pro17Ser (c.49C>T) pathogenic?

FANCL p.Pro17Ser (c.49C>T) is classified Uncertain significance in FANCL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). AlphaMissense: likely pathogenic (0.5806); Absent from gnomAD v4.1.

How common is FANCL p.Pro17Ser (c.49C>T) in the general population?

FANCL p.Pro17Ser (c.49C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FANCL p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely pathogenic (score 0.5806) — an in-silico prediction, not a clinical call.

FANCL p.Pro17Ser

c.49C>T · rs2104081877 · VCV1343688

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5806 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5806	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -11.96	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 82 kb · p 0.00068 · regional, not allelic
Overall
CADD	27.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FANCL
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_018062
dbSNP: rs2104081877
Type: single nucleotide variant
Location: chr2:58241265 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 8 PDB
Residue 17: a β-strand

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

Similar variants

FANCL p.Pro17Arg Uncertain significance ★★ same residue
FANCL p.Pro17= Likely benign ★★ same residue
FANCL c.1021-2A>G Likely pathogenic ★★ same type
FANCL c.1021-2A>T Likely pathogenic ★★ same type
FANCL c.156-2A>T Likely pathogenic ★★ same type
FANCL c.273+1G>A Likely pathogenic ★★ same type
FANCL c.471+2T>C Likely pathogenic ★★ same type
FANCL c.472-1G>C Pathogenic/Likely pathogenic ★★ 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/fancl-p-pro17ser (accessed [today's date]).

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