Is A1CF p.Val159Phe (c.475G>T) pathogenic?

A1CF p.Val159Phe (c.475G>T) is classified Uncertain significance in A1CF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.5991); Ultra-rare (popmax 0.0156%, eas).

How common is A1CF p.Val159Phe (c.475G>T) in the general population?

A1CF p.Val159Phe (c.475G>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about A1CF p.Val159Phe (c.475G>T)?

AlphaMissense predicts likely pathogenic (score 0.5991) — an in-silico prediction, not a clinical call.

A1CF p.Val159Phe

c.475G>T · rs767553962 · VCV2410875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5991	likely pathogenic
REVEL	0.293	indeterminate
SaProt	LLR -12.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 53 kb · p 0.014 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,872 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.0049% 79/1,613,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,410
European (non-Finnish)	0.00576%	17,352
Remaining individualsnot grpmax-eligible	0.0016%	62,482
Finnishnot grpmax-eligible	0.00156%	64,034
African / African-American	0.00133%	74,918
South Asian	0.0011%	91,082

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: A1CF
Protein: p.Val159Phe
Coding: c.475G>T
MANE Select: NM_014576
dbSNP: rs767553962
Type: single nucleotide variant
Location: chr10:50836203 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.70 · 1 PDB
Residue 159: the rrm 2 domain

Full A1CF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

A1CF p.Ala195= Benign ★★ same type
A1CF p.Cys76= Benign ★★ same type
A1CF p.Gly390Ser Likely benign ★★ same type
A1CF p.Ser294= Benign ★★ same type
A1CF c.100-6618G>A Uncertain significance ★ same type
A1CF c.100-6622G>A Uncertain significance ★ same type
A1CF p.Ala383Val Uncertain significance ★ ⚠ same type
A1CF p.Ala462Ser 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/a1cf-p-val159phe (accessed [today's date]).

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