Is APOBEC3F p.Arg208Cys (c.622C>T) pathogenic?

APOBEC3F p.Arg208Cys (c.622C>T) is classified Uncertain significance in APOBEC3F (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.1889); Very rare (popmax 0.000424%, nfe).

How common is APOBEC3F p.Arg208Cys (c.622C>T) in the general population?

APOBEC3F p.Arg208Cys (c.622C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about APOBEC3F p.Arg208Cys (c.622C>T)?

AlphaMissense predicts likely benign (score 0.1889) — an in-silico prediction, not a clinical call.

APOBEC3F p.Arg208Cys

c.622C>T · rs1247334506 · VCV2274716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1889	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.9	GERP -1.9
Regional constraint	o/e 0.97	unconstrained · MANE · 12 kb · p 0.49 · regional, not allelic
Overall
CADD	11.06	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000424% European (non-Finnish) · 5/1,180,020 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,007
European (non-Finnish)grpmax	0.000424%	236,004

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: APOBEC3F
Protein: p.Arg208Cys
Coding: c.622C>T
MANE Select: NM_145298
dbSNP: rs1247334506
Type: single nucleotide variant
Location: chr22:39049480 (GRCh38)
Gene constraint: LOEUF 1.014 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31 · 10 PDB
Residue 208: the cmp/dcmp-type deaminase 2 domain; an α-helix

Full APOBEC3F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3F p.Asn346Ser Benign/Likely benign ★★ same type
APOBEC3F p.Glu151Asp Likely benign ★★ same type
APOBEC3F p.Glu373Lys Likely benign ★★ same type
APOBEC3F p.Pro191= Benign ★★ same type
APOBEC3F p.Tyr307Cys Benign ★★ ⚠ same type
APOBEC3F c.196G>C Uncertain significance ★ ⚠ same type
APOBEC3F p.Arg128Lys Uncertain significance ★ ⚠ same type
APOBEC3F p.Arg143His 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/apobec3f-p-arg208cys (accessed [today's date]).

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