Is MMS19 p.Ala2Val (c.5C>T) pathogenic?

MMS19 p.Ala2Val (c.5C>T) is classified Uncertain significance in MMS19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: ambiguous (0.3568); Very rare (popmax 0.00349%, amr).

How common is MMS19 p.Ala2Val (c.5C>T) in the general population?

MMS19 p.Ala2Val (c.5C>T) is very rare (popmax 0.00349%, amr) (gnomAD).

What do computational predictors say about MMS19 p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.3568) — an in-silico prediction, not a clinical call.

MMS19 p.Ala2Val

c.5C>T · rs1320816020 · VCV2282930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3568 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3568	ambiguous
REVEL	0.2	benign-leaning
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 28 kb · p 0.98 · regional, not allelic
Overall
CADD	23.6	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 0.00349% Admixed American · 2/57,294 alleles

Filtering AF 0.000579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.00035% 5/1,427,540 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00349%	28,647
East Asian	0.0023%	43,474
Remaining individualsnot grpmax-eligible	0.00162%	61,562
European (non-Finnish)	8.54e-05%	1,170,792

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: MMS19
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_022362
dbSNP: rs1320816020
Type: single nucleotide variant
Location: chr10:97498380 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00
Residue 2: a modified residue (n-acetylalanine)

Full MMS19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MMS19 p.Ala656= Likely benign ★★ same type
MMS19 p.Gln409Pro Benign ★★ same type
MMS19 p.Ala11Val Uncertain significance ★ ⚠ same type
MMS19 p.Ala121Ser Uncertain significance ★ ⚠ same type
MMS19 p.Ala324Val Uncertain significance ★ ⚠ same type
MMS19 p.Ala383Val Uncertain significance ★ ⚠ same type
MMS19 p.Ala3Val Uncertain significance ★ ⚠ same type
MMS19 p.Ala4Thr 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/mms19-p-ala2val (accessed [today's date]).

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