Is CEP128 p.Gln371Arg (c.1112A>G) pathogenic?

CEP128 p.Gln371Arg (c.1112A>G) is classified Uncertain significance in CEP128 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.1031); Ultra-rare (popmax 0.0493%, mid).

How common is CEP128 p.Gln371Arg (c.1112A>G) in the general population?

CEP128 p.Gln371Arg (c.1112A>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about CEP128 p.Gln371Arg (c.1112A>G)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

CEP128 p.Gln371Arg

c.1112A>G · rs185240818 · VCV2410915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 419 kb · p 0.4 · regional, not allelic
Overall
CADD	22.0	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00397% 64/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Admixed American	0.0267%	3,750
European (non-Finnish)	0.00364%	27,441
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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: CEP128
Protein: p.Gln371Arg
Coding: c.1112A>G
MANE Select: NM_152446
dbSNP: rs185240818
Type: single nucleotide variant
Location: chr14:80831240 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.92

Full CEP128 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TSHR p.Cys29Ter Pathogenic ★★ same type
TSHR p.Cys29Trp Uncertain significance ★★ ⚠ same type
TSHR p.Leu57Pro Uncertain significance ★★ ⚠ same type
CEP128 p.Gln443Arg Likely benign ★★ same type
CEP128 p.Thr317= Benign ★★ same type
TSHR c.170+10C>T Likely benign ★★ same type
TSHR c.170+16A>C Likely benign ★★ same type
TSHR c.170+63G>C Benign ★★ 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/cep128-p-gln371arg (accessed [today's date]).

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