Is MOCOS p.Ser261Phe (c.782C>T) pathogenic?

MOCOS p.Ser261Phe (c.782C>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely pathogenic (0.9453); Ultra-rare (popmax 0.011%, sas).

How common is MOCOS p.Ser261Phe (c.782C>T) in the general population?

MOCOS p.Ser261Phe (c.782C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about MOCOS p.Ser261Phe (c.782C>T)?

AlphaMissense predicts likely pathogenic (score 0.9453) — an in-silico prediction, not a clinical call.

MOCOS p.Ser261Phe

c.782C>T · rs759627383 · VCV2612222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9453 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9453	likely pathogenic · top 4% in MOCOS
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -13.84	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	31.0	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 0.011% South Asian · 10/91,092 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000619% 10/1,614,242 alleles · ultra-rare exomes 10/1,461,894 · genomes 0/152,348 · 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: MOCOS
Protein: p.Ser261Phe
Coding: c.782C>T
MANE Select: NM_017947
dbSNP: rs759627383
Type: single nucleotide variant
Location: chr18:36200165 (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 p.Ser261= Uncertain significance ★ same residue
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

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-ser261phe (accessed [today's date]).

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