Is SPEG p.Met1908Val (c.5722A>G) pathogenic?

SPEG p.Met1908Val (c.5722A>G) is classified Likely benign in SPEG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0497); Rare (popmax 0.727%, afr); Associated with Inborn genetic diseases.

What condition is associated with SPEG p.Met1908Val (c.5722A>G)?

SPEG p.Met1908Val (c.5722A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SPEG p.Met1908Val (c.5722A>G) in the general population?

SPEG p.Met1908Val (c.5722A>G) is rare (popmax 0.727%, afr) (gnomAD).

What do computational predictors say about SPEG p.Met1908Val (c.5722A>G)?

AlphaMissense predicts likely benign (score 0.0497) — an in-silico prediction, not a clinical call.

SPEG p.Met1908Val

c.5722A>G · rs200747365 · VCV730536

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0497 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.727%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0497	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 0.42, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 7,108 bp · p 0.064 · regional, not allelic
Overall
CADD	8.045	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.727% African / African-American · 545/74,944 alleles

Filtering AF 0.677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.657%

Overall 0.0399% 642/1,609,850 alleles · rare exomes 321/1,457,746 · genomes 321/152,104 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.727%	138
Admixed American	0.0752%	1,330
Remaining individualsnot grpmax-eligible	0.0658%	1,521
Middle Eastern	0.0165%	6,056
South Asian	0.00661%	15,120
European (non-Finnish)	0.000339%	294,770

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: SPEG
Protein: p.Met1908Val
Coding: c.5722A>G
MANE Select: NM_005876
dbSNP: rs200747365
Type: single nucleotide variant
Location: chr2:219483185 (GRCh38)

Full SPEG 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

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/speg-p-met1908val (accessed [today's date]).

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