Is F5 p.Pro1122Ser (c.3364C>T) pathogenic?

F5 p.Pro1122Ser (c.3364C>T) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-11). AlphaMissense: likely benign (0.0742); Ultra-rare (popmax 0.0683%, amr); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro1122Ser (c.3364C>T)?

F5 p.Pro1122Ser (c.3364C>T) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Pro1122Ser (c.3364C>T) in the general population?

F5 p.Pro1122Ser (c.3364C>T) is ultra-rare (popmax 0.0683%, amr) (gnomAD).

What do computational predictors say about F5 p.Pro1122Ser (c.3364C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

F5 p.Pro1122Ser

c.3364C>T · rs185270765 · VCV1730643

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0683%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.23	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 -0.75	GERP -3.4
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	0.345	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 0.0683% Admixed American · 41/59,998 alleles

Filtering AF 0.0517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.007% 113/1,613,940 alleles · ultra-rare exomes 102/1,461,696 · genomes 11/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0683%	1,463
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.00568%	17,611
African / African-American	0.00133%	75,032

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: F5
Protein: p.Pro1122Ser
Coding: c.3364C>T
MANE Select: NM_000130
dbSNP: rs185270765
Type: single nucleotide variant
Location: chr1:169541726 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1122: the 'b' region; the 'disordered' region

Full F5 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

Similar variants

F5 p.Pro1122His Uncertain significance ★ ⚠ same residue
F5 p.Arg441His Uncertain significance ★★ ⚠ same condition
F5 p.Asn1559Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asn1575Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asp1739Gly Uncertain significance ★★ ⚠ same condition
F5 p.Glu2029Asp Uncertain significance ★★ ⚠ same condition
F5 p.Glu48Gln Uncertain significance ★★ ⚠ same condition
F5 p.His812Tyr 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/f5-p-pro1122ser (accessed [today's date]).

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