Is CERS6 p.Pro62Arg (c.185C>G) pathogenic?

CERS6 p.Pro62Arg (c.185C>G) is classified Uncertain significance in CERS6 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.63); Rare (popmax 0.111%, nfe).

How common is CERS6 p.Pro62Arg (c.185C>G) in the general population?

CERS6 p.Pro62Arg (c.185C>G) is rare (popmax 0.111%, nfe) (gnomAD).

What do computational predictors say about CERS6 p.Pro62Arg (c.185C>G)?

AlphaMissense predicts likely pathogenic (score 0.63) — an in-silico prediction, not a clinical call.

CERS6 p.Pro62Arg

c.185C>G · rs146638314 · VCV3143186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.63 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.63	likely pathogenic
REVEL	0.674	pathogenic-leaning
SaProt	LLR -11.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 313 kb · p 0.015 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.111% European (non-Finnish) · 1,305/1,178,810 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0877% 1,415/1,612,766 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.111%	903
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,741
Admixed American	0.0533%	1,875
African / African-American	0.02%	5,001
Finnishnot grpmax-eligible	0.00469%	21,337

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: CERS6
Protein: p.Pro62Arg
Coding: c.185C>G
MANE Select: NM_203463
dbSNP: rs146638314
Type: single nucleotide variant
Location: chr2:168547610 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 87.97 · 3 PDB
Residue 62: an α-helix

Full CERS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS6 p.Pro62Ser Uncertain significance ★ ⚠ same residue
CERS6 p.Ala30Ser Uncertain significance ★ ⚠ same type
CERS6 p.Ala326Val Uncertain significance ★ ⚠ same type
CERS6 p.Ala362Val Uncertain significance ★ ⚠ same type
CERS6 p.Ala6Val Uncertain significance ★ ⚠ same type
CERS6 p.Arg121Cys Uncertain significance ★ ⚠ same type
CERS6 p.Asn10Lys Uncertain significance ★ ⚠ same type
CERS6 p.Asn122Ser 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/cers6-p-pro62arg (accessed [today's date]).

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