Is F8 p.Ala167Val (c.500C>T) pathogenic?

F8 p.Ala167Val (c.500C>T) is classified Uncertain significance in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.1157); Ultra-rare (popmax 0.0105%, sas); Associated with Inborn genetic diseases.

What condition is associated with F8 p.Ala167Val (c.500C>T)?

F8 p.Ala167Val (c.500C>T) is associated with Inborn genetic diseases (ClinVar).

How common is F8 p.Ala167Val (c.500C>T) in the general population?

F8 p.Ala167Val (c.500C>T) is ultra-rare (popmax 0.0105%, sas) (gnomAD).

What do computational predictors say about F8 p.Ala167Val (c.500C>T)?

AlphaMissense predicts likely benign (score 0.1157) — an in-silico prediction, not a clinical call.

F8 p.Ala167Val

c.500C>T · VCV3277001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1157 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1157	likely benign
REVEL	0.694	pathogenic-leaning
SaProt	LLR -7.66	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 5.9	GERP -1.3, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 53 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	20.1	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

Grpmax group 0.0105% South Asian · 6/56,993 alleles

Filtering AF 0.00457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.00066% 8/1,211,282 alleles · ultra-rare exomes 8/1,097,562 · genomes 0/113,720 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0105%	9,499
Remaining individualsnot grpmax-eligible	0.0021%	47,632
African / African-American	0.00173%	57,831

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: F8
Protein: p.Ala167Val
Coding: c.500C>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154993037 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 167: a β-strand; the f5/8 type a 1 domain; the plastocyanin-like 1 domain

Full F8 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

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F8 p.Gly1729Trp Uncertain significance ★★ ⚠ same condition
F8 p.Leu13Phe Uncertain significance ★★ ⚠ same condition
F8 p.Ser1968Asn Uncertain significance ★★ ⚠ same condition
F8 p.Thr1670Ile 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/f8-p-ala167val (accessed [today's date]).

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