Is MOCOS p.Pro283Ser (c.847C>T) pathogenic?

MOCOS p.Pro283Ser (c.847C>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: likely benign (0.0726); Ultra-rare (popmax 0.0134%, eas).

How common is MOCOS p.Pro283Ser (c.847C>T) in the general population?

MOCOS p.Pro283Ser (c.847C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about MOCOS p.Pro283Ser (c.847C>T)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

MOCOS p.Pro283Ser

c.847C>T · rs776832613 · VCV3188929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.16	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 2.2	GERP 0.065, phastCons 0.94
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	12.47	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 0.0134% East Asian · 6/44,892 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000682% 11/1,614,008 alleles · ultra-rare exomes 8/1,461,840 · genomes 3/152,168 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,482
African / African-American	0.00267%	37,456
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.47e-05%	1,180,002

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: MOCOS
Protein: p.Pro283Ser
Coding: c.847C>T
MANE Select: NM_017947
dbSNP: rs776832613
Type: single nucleotide variant
Location: chr18:36200230 (GRCh38)
Gene constraint: LOEUF 1.19 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.88

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

Similar variants

MOCOS c.1218+1G>C Likely pathogenic ★★ same type
MOCOS c.2164+2T>C Likely pathogenic ★★ same type
MOCOS c.232+1G>A Likely pathogenic ★★ same type
MOCOS p.Arg419Ter Pathogenic ★★ same type
MOCOS p.Arg776Cys Pathogenic/Likely pathogenic ★★ same type
MOCOS p.Gln516Ter Likely pathogenic ★★ same type
MOCOS p.Glu42Ter Likely pathogenic ★★ same type
MOCOS p.Glu763Ter Likely pathogenic ★★ 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/mocos-p-pro283ser (accessed [today's date]).

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