Is F7 p.Pro48Ser (c.142C>T) pathogenic?

F7 p.Pro48Ser (c.142C>T) is classified Conflicting classifications of pathogenicity in F7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.1073); Ultra-rare (popmax 0.0676%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F7 p.Pro48Ser (c.142C>T)?

F7 p.Pro48Ser (c.142C>T) is associated with Inborn genetic diseases, congenital factor VII deficiency (ClinVar).

How common is F7 p.Pro48Ser (c.142C>T) in the general population?

F7 p.Pro48Ser (c.142C>T) is ultra-rare (popmax 0.0676%, nfe) (gnomAD).

What do computational predictors say about F7 p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely benign (score 0.1073) — an in-silico prediction, not a clinical call.

F7 p.Pro48Ser

c.142C>T · rs373376565 · VCV1703844

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0676%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1073	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -11.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -3.8
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	2.085	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P70S vs ClinVar P48S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0676% European (non-Finnish) · 775/1,147,078 alleles

Filtering AF 0.0636% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.062%

Overall 0.0543% 842/1,549,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0676%	1,480
East Asian	0.0415%	2,409
Remaining individualsnot grpmax-eligible	0.03%	3,333
African / African-American	0.0191%	5,228
Admixed American	0.0157%	6,386
Ashkenazi Jewishnot grpmax-eligible	0.00699%	14,315
South Asian	0.00595%	16,810
Finnishnot grpmax-eligible	0.00509%	19,640

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: F7
Protein: p.Pro48Ser
Coding: c.142C>T
MANE Select: NM_019616
dbSNP: rs373376565
Type: single nucleotide variant
Location: chr13:113110767 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB

Full F7 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: congenital factor VII deficiency

Similar variants

F7 c.225+1G>C Pathogenic ★★ same condition
F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.505+78G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.739+1G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.-30A>C Likely pathogenic ★★ same condition
F7 c.-55C>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.-61T>G Likely pathogenic ★★ 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/f7-p-pro48ser (accessed [today's date]).

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