Is SLMAP p.Gly77Asp (c.230G>A) pathogenic?

SLMAP p.Gly77Asp (c.230G>A) is classified Uncertain significance in SLMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). AlphaMissense: likely pathogenic (1); Very rare (popmax 8.63e-05%, nfe).

How common is SLMAP p.Gly77Asp (c.230G>A) in the general population?

SLMAP p.Gly77Asp (c.230G>A) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

What do computational predictors say about SLMAP p.Gly77Asp (c.230G>A)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

SLMAP p.Gly77Asp

c.230G>A · rs2472134982 · VCV2447996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic · top 2% in SLMAP
REVEL	0.799	moderately pathogenic-leaning
SaProt	LLR -18.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 74 kb · p 4.7e-09 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,159,216 alleles

Overall 6.37e-05% 1/1,570,486 alleles · very rare exomes 1/1,418,530 · genomes 0/151,956 · joint denominator

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: SLMAP
Protein: p.Gly77Asp
Coding: c.230G>A
MANE Select: NM_001377540
dbSNP: rs2472134982
Type: single nucleotide variant
Location: chr3:57831414 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.74 · 3 PDB
Residue 77: the fha domain; the 'necessary for targeting to centrosomes' region

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

Similar variants

SLMAP c.*38C>T Uncertain significance ★★ ⚠ same type
SLMAP c.*55G>A Uncertain significance ★★ ⚠ same type
SLMAP c.*70G>A Uncertain significance ★★ ⚠ same type
SLMAP p.Ala365Asp Uncertain significance ★★ ⚠ same type
SLMAP p.Ala506Ser Uncertain significance ★★ ⚠ same type
SLMAP p.Ala597Val Uncertain significance ★★ ⚠ same type
SLMAP p.Arg136Gln Uncertain significance ★★ ⚠ same type
SLMAP p.Arg138Cys 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/slmap-p-gly77asp (accessed [today's date]).

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