Is F3 p.Ile54Val (c.160A>G) pathogenic?

F3 p.Ile54Val (c.160A>G) is classified Likely benign in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-19). AlphaMissense: likely benign (0.1671); Rare (popmax 0.841%, afr).

How common is F3 p.Ile54Val (c.160A>G) in the general population?

F3 p.Ile54Val (c.160A>G) is rare (popmax 0.841%, afr) (gnomAD).

What do computational predictors say about F3 p.Ile54Val (c.160A>G)?

AlphaMissense predicts likely benign (score 0.1671) — an in-silico prediction, not a clinical call.

F3 p.Ile54Val

c.160A>G · rs114064069 · VCV789150

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1671 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.841%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1671	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.63 · regional, not allelic
Overall
CADD	23.4	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 0.841% African / African-American · 631/75,044 alleles

Filtering AF 0.787% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.765%

Overall 0.062% 1,000/1,614,108 alleles · rare exomes 626/1,461,772 · genomes 374/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.841%	119
Middle Eastern	0.214%	466
Admixed American	0.133%	750
Remaining individualsnot grpmax-eligible	0.0944%	1,059
European (non-Finnish)	0.0176%	5,673
South Asian	0.00988%	10,120

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: F3
Protein: p.Ile54Val
Coding: c.160A>G
MANE Select: NM_001993
dbSNP: rs114064069
Type: single nucleotide variant
Location: chr1:94540309 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40 · 54 PDB
Residue 54: a β-strand

Full F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F3 p.Arg163Trp Benign ★★ ⚠ same type
F3 p.Gly281Glu Benign ★★ same type
F3 p.Thr36Ala Benign ★★ same type
F3 p.Ala17Thr Uncertain significance ★ ⚠ same type
F3 p.Ala30Thr Uncertain significance ★ ⚠ same type
F3 p.Arg11His Uncertain significance ★ ⚠ same type
F3 p.Arg176Trp Uncertain significance ★ same type
F3 p.Arg228Gln Uncertain significance ★ 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/f3-p-ile54val (accessed [today's date]).

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