Is SMS p.Pro112Gln (c.335C>A) pathogenic?

SMS p.Pro112Gln (c.335C>A) is classified Likely pathogenic in SMS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely pathogenic (0.6619); No allele count reported in gnomAD v4.1 (AN 1,209,327); Associated with syndromic X-linked intellectual disability Snyder type.

What condition is associated with SMS p.Pro112Gln (c.335C>A)?

SMS p.Pro112Gln (c.335C>A) is associated with syndromic X-linked intellectual disability Snyder type (ClinVar).

How common is SMS p.Pro112Gln (c.335C>A) in the general population?

SMS p.Pro112Gln (c.335C>A) is no allele count reported in gnomAD v4.1 (AN 1,209,327) (gnomAD).

How is X-linked intellectual disability, Snyder type inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SMS p.Pro112Gln (c.335C>A)?

AlphaMissense predicts likely pathogenic (score 0.6619) — an in-silico prediction, not a clinical call.

SMS p.Pro112Gln

c.335C>A · rs2147517480 · VCV2444331

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6619 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,209,327)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Snyder type

Computational evidence

Protein change
AlphaMissense	0.6619	likely pathogenic ✓ concordant with ClinVar
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -2.83	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 22 kb · p 3.7e-21 · regional, not allelic
Overall
CADD	26.3	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

No allele count reported in gnomAD v4.1 (AN 1,209,327). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SMS
Protein: p.Pro112Gln
Coding: c.335C>A
MANE Select: NM_004595
dbSNP: rs2147517480
Type: single nucleotide variant
Location: chrX:21977066 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 112: an α-helix

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

Disease context

syndromic X-linked intellectual disability Snyder type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked intellectual disability, Snyder type (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

SMS p.Pro112Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
SMS p.Arg234Ter Pathogenic/Likely pathogenic ★★ same condition
SMS p.Gly203Asp Pathogenic ★★ same condition
SMS p.Gly56Ser Pathogenic ★★ ⚠ same condition
SMS p.Ile196Thr Likely pathogenic ★★ same condition
SMS c.1061+2T>C Uncertain significance ★★ same condition
SMS p.Gly333Arg Uncertain significance ★★ ⚠ same condition
SMS p.Gly78Ala 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/sms-p-pro112gln (accessed [today's date]).

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