Is PRR12 p.Ala1663Thr (c.4987G>A) pathogenic?

PRR12 p.Ala1663Thr (c.4987G>A) is classified Likely benign in PRR12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: ambiguous (0.3608); Very rare (popmax 0.00356%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRR12 p.Ala1663Thr (c.4987G>A)?

PRR12 p.Ala1663Thr (c.4987G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PRR12 p.Ala1663Thr (c.4987G>A) in the general population?

PRR12 p.Ala1663Thr (c.4987G>A) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about PRR12 p.Ala1663Thr (c.4987G>A)?

AlphaMissense predicts ambiguous (score 0.3608) — an in-silico prediction, not a clinical call.

PRR12 p.Ala1663Thr

c.4987G>A · rs749294900 · VCV2396267

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3608	ambiguous
REVEL	0.082	moderately benign-leaning
SaProt	LLR -4.30	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP -3.7, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 13 kb · p 4.8e-10 · regional, not allelic
Overall
CADD	25.4	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 0.00356% European (non-Finnish) · 42/1,179,910 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00266% 43/1,613,914 alleles · very rare exomes 42/1,461,690 · genomes 1/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,093
South Asian	0.0011%	91,092

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: PRR12
Protein: p.Ala1663Thr
Coding: c.4987G>A
MANE Select: NM_020719
dbSNP: rs749294900
Type: single nucleotide variant
Location: chr19:49614972 (GRCh38)
Gene constraint: LOEUF 0.18 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.84
Residue 1663: a UniProt-annotated variant site (in noc1)

Full PRR12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRR12 p.Ala1190Ser Uncertain significance ★★ ⚠ same condition
PRR12 p.Ala82Gly Uncertain significance ★★ ⚠ same condition
PRR12 p.Arg1755Gln Uncertain significance ★★ ⚠ same condition
PRR12 p.Asp1109Tyr Uncertain significance ★★ ⚠ same condition
PRR12 p.Glu1100Lys Uncertain significance ★★ ⚠ same condition
PRR12 p.Glu943Ala Uncertain significance ★★ ⚠ same condition
PRR12 p.Gly1566Ser Uncertain significance ★★ ⚠ same condition
PRR12 p.Gly963Ser Uncertain significance ★★ ⚠ same condition

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/prr12-p-ala1663thr (accessed [today's date]).

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