Is MOCOS p.Ala2Val (c.5C>T) pathogenic?

MOCOS p.Ala2Val (c.5C>T) is classified Uncertain significance in MOCOS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.5495); Very rare (popmax 0.00314%, eas).

How common is MOCOS p.Ala2Val (c.5C>T) in the general population?

MOCOS p.Ala2Val (c.5C>T) is very rare (popmax 0.00314%, eas) (gnomAD).

What do computational predictors say about MOCOS p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.5495) — an in-silico prediction, not a clinical call.

MOCOS p.Ala2Val

c.5C>T · VCV3912353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5495	ambiguous
REVEL	0.085	moderately benign-leaning
SaProt	LLR -8.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.67, phastCons 0.72
Regional constraint	o/e 0.99	unconstrained · MANE · 81 kb · p 0.84 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% East Asian · 1/31,846 alleles

Overall 0.000162% 2/1,237,092 alleles · very rare exomes 2/1,084,904 · genomes 0/152,188 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00314%	31,846
Remaining individualsnot grpmax-eligible	0.00218%	45,886

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_017947
Type: single nucleotide variant
Location: chr18:36187544 (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.Ala2Thr 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-ala2val (accessed [today's date]).

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