Is PRMT7 p.Val649Ile (c.1945G>A) pathogenic?

PRMT7 p.Val649Ile (c.1945G>A) is classified Conflicting classifications of pathogenicity in PRMT7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-15). AlphaMissense: likely benign (0.1586); Rare (popmax 0.241%, eas); Associated with short stature-brachydactyly-obesity-global developmental delay syndrome.

What condition is associated with PRMT7 p.Val649Ile (c.1945G>A)?

PRMT7 p.Val649Ile (c.1945G>A) is associated with short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

How common is PRMT7 p.Val649Ile (c.1945G>A) in the general population?

PRMT7 p.Val649Ile (c.1945G>A) is rare (popmax 0.241%, eas) (gnomAD).

What do computational predictors say about PRMT7 p.Val649Ile (c.1945G>A)?

AlphaMissense predicts likely benign (score 0.1586) — an in-silico prediction, not a clinical call.

PRMT7 p.Val649Ile

c.1945G>A · rs143131470 · VCV715535

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1586 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.241%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short stature-brachydactyly-obesity-global developmental delay syndrome

Computational evidence

Protein change
AlphaMissense	0.1586	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -9.28	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	25.5	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 0.241% East Asian · 108/44,874 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.0136% 219/1,612,956 alleles · rare exomes 177/1,460,636 · genomes 42/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.241%	415
Remaining individualsnot grpmax-eligible	0.0656%	1,524
African / African-American	0.0227%	4,413
Middle Eastern	0.0165%	6,062
South Asian	0.0154%	6,497
Admixed American	0.00501%	19,949
European (non-Finnish)	0.00288%	34,692
Finnishnot grpmax-eligible	0.00157%	63,716

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: PRMT7
Protein: p.Val649Ile
Coding: c.1945G>A
MANE Select: NM_019023
dbSNP: rs143131470
Type: single nucleotide variant
Location: chr16:68357090 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 649: the sam-dependent mtase prmt-type 2 domain

Full PRMT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short stature-brachydactyly-obesity-global developmental delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRMT7 c.1056-1G>T Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg390Ter Pathogenic ★★ same condition
PRMT7 p.Cys571Ter Pathogenic ★★ same condition
PRMT7 p.Gln323Ter Pathogenic ★★ same condition
PRMT7 p.Glu108Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Tyr159Ter Pathogenic ★★ same condition
PRMT7 p.Arg360Cys 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/prmt7-p-val649ile (accessed [today's date]).

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