Is A1CF p.His488Pro (c.1463A>C) pathogenic?

A1CF p.His488Pro (c.1463A>C) is classified Uncertain significance in A1CF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.1639); Very rare (popmax 0.0011%, sas).

How common is A1CF p.His488Pro (c.1463A>C) in the general population?

A1CF p.His488Pro (c.1463A>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about A1CF p.His488Pro (c.1463A>C)?

AlphaMissense predicts likely benign (score 0.1639) — an in-silico prediction, not a clinical call.

A1CF p.His488Pro

c.1463A>C · rs771577560 · VCV2242854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1639	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -12.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 53 kb · p 0.014 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM H496P vs ClinVar H488P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,056 alleles

Overall 6.2e-05% 1/1,613,784 alleles · very rare exomes 1/1,461,556 · genomes 0/152,228 · joint denominator

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.His488Pro
Coding: c.1463A>C
MANE Select: NM_014576
dbSNP: rs771577560
Type: single nucleotide variant
Location: chr10:50810040 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.70 · 1 PDB

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-his488pro (accessed [today's date]).

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