Is F2 p.Leu210Ser (c.629T>C) pathogenic?

F2 p.Leu210Ser (c.629T>C) is classified Conflicting classifications of pathogenicity in F2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-30). AlphaMissense: likely benign (0.0498); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with F2 p.Leu210Ser (c.629T>C)?

F2 p.Leu210Ser (c.629T>C) is associated with Inborn genetic diseases, congenital prothrombin deficiency (ClinVar).

How common is F2 p.Leu210Ser (c.629T>C) in the general population?

F2 p.Leu210Ser (c.629T>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about F2 p.Leu210Ser (c.629T>C)?

AlphaMissense predicts likely benign (score 0.0498) — an in-silico prediction, not a clinical call.

F2 p.Leu210Ser

c.629T>C · rs948273916 · VCV3091424

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0498	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -4.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -2.9
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	0.003	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 0.004% African / African-American · 3/74,914 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,736 alleles · very rare

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: F2
Protein: p.Leu210Ser
Coding: c.629T>C
MANE Select: NM_000506
dbSNP: rs948273916
Type: single nucleotide variant
Location: chr11:46725928 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB

Full F2 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 prothrombin deficiency

Similar variants

F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg500Gln Pathogenic ★★ ⚠ same condition
F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg596Gln Pathogenic ★★ ⚠ same condition
F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same condition
F2 c.559+5G>A Uncertain significance ★★ same condition
F2 p.Ala17Ser Uncertain significance ★★ ⚠ same condition
F2 p.Ala490Thr 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/f2-p-leu210ser (accessed [today's date]).

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