Is ORC6 p.Ser57= (c.171C>G) pathogenic?

ORC6 p.Ser57= (c.171C>G) is classified Likely benign in ORC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). Very rare (popmax 0.004%, afr).

How common is ORC6 p.Ser57= (c.171C>G) in the general population?

ORC6 p.Ser57= (c.171C>G) is very rare (popmax 0.004%, afr) (gnomAD).

ORC6 p.Ser57=

c.171C>G · rs143555249 · VCV2992099

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 1.4	GERP 5, phastCons 0.92
Overall
CADD	13.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,948 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,070 alleles · very rare exomes 2/1,461,874 · genomes 1/152,196 · 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: ORC6
Protein: p.Ser57=
Coding: c.171C>G
MANE Select: NM_014321
dbSNP: rs143555249
Type: single nucleotide variant
Location: chr16:46691096 (GRCh38)
Gene constraint: LOEUF 1.784 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.69 · 4 PDB
Residue 57: an α-helix

Full ORC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ORC6 p.Ser57Thr Uncertain significance ★ ⚠ same residue
ORC6 p.Ala10Ser Uncertain significance ★★ ⚠ same type
ORC6 p.Arg8His Uncertain significance ★★ ⚠ same type
ORC6 p.Arg8Leu Uncertain significance ★★ ⚠ same type
ORC6 p.Gln130His Uncertain significance ★★ ⚠ same type
ORC6 p.Ile69Met Uncertain significance ★★ ⚠ same type
ORC6 p.Leu228Val Uncertain significance ★★ ⚠ same type
ORC6 p.Leu92Pro 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/orc6-p-ser57 (accessed [today's date]).

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