Is APOBEC3H p.Arg17Cys (c.49C>T) pathogenic?

APOBEC3H p.Arg17Cys (c.49C>T) is classified Uncertain significance in APOBEC3H (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.1919); Ultra-rare (popmax 0.0164%, mid).

How common is APOBEC3H p.Arg17Cys (c.49C>T) in the general population?

APOBEC3H p.Arg17Cys (c.49C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about APOBEC3H p.Arg17Cys (c.49C>T)?

AlphaMissense predicts likely benign (score 0.1919) — an in-silico prediction, not a clinical call.

APOBEC3H p.Arg17Cys

c.49C>T · rs374766186 · VCV3127973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1919	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -1.3
Regional constraint	o/e 1.00	unconstrained · MANE · 3,415 bp · p 0.95 · regional, not allelic
Overall
CADD	17.44	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00564% 91/1,613,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00801%	12,479
European (non-Finnish)	0.00653%	15,324
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,982
Finnishnot grpmax-eligible	0.00156%	64,012
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: APOBEC3H
Protein: p.Arg17Cys
Coding: c.49C>T
MANE Select: NM_181773
dbSNP: rs374766186
Type: single nucleotide variant
Location: chr22:39100327 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 89.41 · 4 PDB
Residue 17: the cmp/dcmp-type deaminase domain

Full APOBEC3H gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3H p.Arg17His Uncertain significance ★ ⚠ same residue
APOBEC3H p.Phe107= Benign ★★ same type
APOBEC3H p.Arg10Cys Uncertain significance ★ ⚠ same type
APOBEC3H p.Arg10His Uncertain significance ★ ⚠ same type
APOBEC3H p.Arg110His Uncertain significance ★ ⚠ same type
APOBEC3H p.Cys116Trp Uncertain significance ★ ⚠ same type
APOBEC3H p.Glu146Gly Uncertain significance ★ ⚠ same type
APOBEC3H p.Glu48Gly 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/apobec3h-p-arg17cys (accessed [today's date]).

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