Is F5 p.Ser262Leu (c.785C>T) pathogenic?

F5 p.Ser262Leu (c.785C>T) is classified Likely pathogenic in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-09). AlphaMissense: likely benign (0.2839); Very rare (popmax 0.00401%, afr); Associated with F5-related disorders.

What condition is associated with F5 p.Ser262Leu (c.785C>T)?

F5 p.Ser262Leu (c.785C>T) is associated with F5-related disorders (ClinVar).

How common is F5 p.Ser262Leu (c.785C>T) in the general population?

F5 p.Ser262Leu (c.785C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about F5 p.Ser262Leu (c.785C>T)?

AlphaMissense predicts likely benign (score 0.2839) — an in-silico prediction, not a clinical call.

F5 p.Ser262Leu

c.785C>T · VCV4921157

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

F5-related disorders

Computational evidence

Protein change
AlphaMissense	0.2839	likely benign ⚠ discordant with ClinVar
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -6.24	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	29.8	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 0.00401% African / African-American · 3/74,884 alleles

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

Overall 0.000434% 7/1,613,922 alleles · very rare exomes 4/1,461,820 · genomes 3/152,102 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,961
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000254%	393,332

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.Ser262Leu
Coding: c.785C>T
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169556813 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 262: the f5/8 type a 1 domain; the plastocyanin-like 2 domain

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

F5-related disorders

Similar variants

F5 p.Ser262= Likely benign ★ same residue
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Thr986Ile Uncertain significance ★★ ⚠ same condition
F5 p.Gln1435Ter Likely pathogenic ★ same condition
F5 p.Gly867Ter Pathogenic ★ same condition
F5 p.Arg1631His Uncertain significance ★ ⚠ same condition
F5 p.Arg534= Conflicting classifications of pathogenicity ★ same condition
F5 p.Asn2190Lys 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-ser262leu (accessed [today's date]).

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