Is A1CF p.Ala195= (c.585G>A) pathogenic?

A1CF p.Ala195= (c.585G>A) is classified Benign in A1CF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-31). Common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele.

A1CF p.Ala195=

Q: How common is A1CF p.Ala195= (c.585G>A) in the general population?

A1CF p.Ala195= (c.585G>A) is common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.585G>A · rs61742973 · VCV786157

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -3.1, phastCons 0.006
Overall
CADD	7.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% African / African-American · 4,289/74,864 alleles

Filtering AF 5.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.53%

Overall 0.32% 5,158/1,610,478 alleles · common exomes 2,655/1,458,168 · genomes 2,503/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.73%	17
Admixed American	0.522%	192
Remaining individualsnot grpmax-eligible	0.367%	272
Middle Eastern	0.182%	549
Ashkenazi Jewishnot grpmax-eligible	0.119%	841
European (non-Finnish)	0.0232%	4,316
South Asian	0.00885%	11,302
East Asian	0.00447%	22,382

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.Ala195=
Coding: c.585G>A
MANE Select: NM_014576
dbSNP: rs61742973
Type: single nucleotide variant
Location: chr10:50836093 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.70 · 1 PDB
Residue 195: the rrm 2 domain

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

Similar variants

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
A1CF p.Ala497Ser 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-ala195 (accessed [today's date]).

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