Is F8 p.Val1981Met (c.5941G>A) pathogenic?

F8 p.Val1981Met (c.5941G>A) is classified Likely pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-31). AlphaMissense: likely benign (0.2997); Absent from gnomAD v4.1.

How common is F8 p.Val1981Met (c.5941G>A) in the general population?

F8 p.Val1981Met (c.5941G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Val1981Met (c.5941G>A)?

AlphaMissense predicts likely benign (score 0.2997) — an in-silico prediction, not a clinical call.

F8 p.Val1981Met

c.5941G>A · rs2073023240 · VCV2920840

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2997	likely benign ⚠ discordant with ClinVar
REVEL	0.603	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 91 kb · p 1.5e-14 · regional, not allelic
Overall
CADD	22.1	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: F8
Protein: p.Val1981Met
Coding: c.5941G>A
MANE Select: NM_000132
dbSNP: rs2073023240
Type: single nucleotide variant
Location: chrX:154903963 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1981: the f5/8 type a 3 domain; the plastocyanin-like 6 domain

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F8 c.6429+2T>A Pathogenic ★★★ same type
F8 p.Ala111Thr Likely pathogenic ★★★ same type
F8 p.Ala2220Pro Pathogenic ★★★ same type
F8 p.Ala415Asp Likely pathogenic ★★★ same type
F8 p.Ala415Val Pathogenic ★★★ ⚠ same type
F8 p.Arg1768His Pathogenic ★★★ ⚠ same type
F8 p.Arg1800His Pathogenic ★★★ same type
F8 p.Arg2016Trp 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/f8-p-val1981met (accessed [today's date]).

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